Intraocular shunt placement in the suprachoroidal space

ABSTRACT

Glaucoma can be treated by implanting an intraocular shunt into the eye. Such procedures can employ various deployment devices, shunts, and implantation techniques. A method for treating glaucoma can include injecting a drug into the eye and positioning an intraocular shunt in eye tissue such that the shunt conducts fluid from the anterior chamber to the suprachoroidal space.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/313,970, filed Jun. 24, 2014; U.S. patent application Ser. No.14/313,970 is a continuation-in-part of U.S. patent application Ser. No.12/946,572, filed on Nov. 15, 2010, now U.S. Pat. No. 8,852,256; U.S.patent application Ser. No. 14/313,970 is also a continuation-in-part ofU.S. patent application Ser. No. 12/946,222, filed on Nov. 15, 2010, nowabandoned; U.S. patent application Ser. No. 14/313,970 is also acontinuation-in-part of U.S. patent application Ser. No. 12/946,240,filed on Nov. 15, 2010, now U.S. Pat. No. 8,828,070; U.S. patentapplication Ser. No. 14/313,970 is also a continuation-in-part of U.S.patent application Ser. No. 12/946,251, filed on Nov. 15, 2010, now U.S.Pat. No. 9,095,411; U.S. patent application Ser. No. 14/313,970 is alsoa continuation-in-part of U.S. patent application Ser. No. 12/946,263,filed on Nov. 15, 2010, now U.S. Pat. No. 8,801,766; U.S. patentapplication Ser. No. 14/313,970 is also a continuation-in-part of U.S.patent application Ser. No. 13/314,927, filed Dec. 8, 2011, nowabandoned, which is a continuation-in-part of U.S. patent applicationSer. No. 12/946,351, filed on Nov. 15, 2010, now abandoned; U.S. patentapplication Ser. No. 14/313,970 is also a continuation-in-part of U.S.patent application Ser. No. 12/946,556, filed on Nov. 15, 2010, nowabandoned; U.S. patent application Ser. No. 14/313,970 is also acontinuation-in-part of U.S. patent application Ser. No. 14/263,957,filed on Apr. 28, 2014, now U.S. Pat. No. 9,283,116, which is acontinuation of U.S. patent application Ser. No. 12/946,645, filed onNov. 15, 2010, now U.S. Pat. No. 8,721,702; U.S. patent application Ser.No. 14/313,970 is also a continuation-in-part of U.S. patent applicationSer. No. 14/191,340, filed on Feb. 26, 2014, now U.S. Pat. No.9,192,516, which is a continuation of U.S. patent application Ser. No.12/946,653, filed on Nov. 15, 2010, now U.S. Pat. No. 8,663,303; U.S.patent application Ser. No. 14/313,970 is also a continuation-in-part ofU.S. patent application Ser. No. 12/946,565, filed on Nov. 15, 2010, nowU.S. Pat. No. 8,974,511; U.S. patent application Ser. No. 14/313,970 isalso a continuation-in-part of U.S. patent application Ser. No.13/336,758, filed on Dec. 23, 2011, now U.S. Pat. No. 8,852,137, whichis a continuation-in-part of U.S. patent application Ser. No.12/946,351, filed on Nov. 15, 2010, now abandoned, and which is acontinuation-in-part of U.S. patent application Ser. No. 12/946,222,filed on Nov. 15, 2010, now abandoned; U.S. patent application Ser. No.14/313,970 is also a continuation-in-part of U.S. patent applicationSer. No. 13/336,803, filed on Dec. 23, 2011, now U.S. Pat. No.8,758,290, which is a continuation-in-part of U.S. patent applicationSer. No. 12/946,351, filed on Nov. 15, 2010, now abandoned, and which isa continuation-in-part of U.S. patent application Ser. No. 12/946,222,filed on Nov. 15, 2010, now abandoned; U.S. patent application Ser. No.14/313,970 is also a continuation-in-part of U.S. patent applicationSer. No. 13/895,170, filed on May 15, 2013, which is a continuation ofInternational Pat. App. No. PCT/US2011/060820, filed on Nov. 15, 2011,which claims the benefit of and priority to U.S. patent application Ser.No. 12/946,210, filed on Nov. 15, 2010, now U.S. Pat. No. 8,308,701; andU.S. patent application Ser. No. 14/313,970 is also acontinuation-in-part of U.S. patent application Ser. No. 13/952,543,filed on Jul. 26, 2013, now U.S. Pat. No. 9,017,276, which is acontinuation of U.S. patent application Ser. No. 12/946,542, filed onNov. 15, 2010, now abandoned; the entireties of each of theseapplications and patents are incorporated herein by reference.

BACKGROUND

1. Field of the Inventions

The present inventions generally relate to surgical methods,implantation devices, and shunts that can be used to treat glaucoma.

2. Description of the Related Art

Glaucoma is a disease of the eye that affects millions of people.Glaucoma is associated with an increase in intraocular pressureresulting either from a failure of a drainage system of an eye toadequately remove aqueous humor from an anterior chamber of the eye oroverproduction of aqueous humor by a ciliary body in the eye. Build-upof aqueous humor and resulting intraocular pressure may result inirreversible damage to the optic nerve and the retina, which may lead toirreversible retinal damage and blindness. Glaucoma affects 1 in 200people aged fifty and younger, and 1 in 10 over the age of eighty for atotal of approximately 70 million people worldwide, and glaucoma is thesecond leading cause of blindness in the world.

There are two main types of glaucoma, “open angle” and “closed angle”glaucoma. Open angle glaucoma refers to glaucoma cases in whichintraocular pressure increases but an anterior chamber angle (drainageangle) of an eye remains open. A common cause of open angle glaucoma isblockage in the trabecular meshwork, the fluid flow pathways thatnormally drain aqueous humor from the anterior chamber of the eye.Closed angle glaucoma refers to glaucoma cases in which intraocularpressure increases due to partial or complete closure of the anteriorchamber angle. In closed angle glaucoma, swelling or movement of theiris closes the anterior chamber angle and blocks fluid from accessingto the trabecular meshwork, which in turn obstructs outflow of theaqueous humor from the eye.

Generally, glaucoma may be treated by surgical intervention thatinvolves placing a shunt in the eye to result in production of fluidflow pathways between the anterior chamber and various structures of theeye involved in aqueous humor drainage (e.g., Schlemm's canal, thesclera, or the subconjunctival space). Such fluid flow pathways allowfor aqueous humor to exit the anterior chamber. Generally, the surgicalintervention to implant the shunt involves inserting into the eye adelivery device that holds an intraocular shunt, and deploying the shuntwithin the eye.

A delivery device holding the shunt enters the eye through a cornea (abinterno approach), and is advanced across the anterior chamber. Thedelivery device is advanced through the sclera until a distal portion ofthe device is in proximity to a drainage structure of the eye. The shuntis then deployed from the delivery device, producing a conduit betweenthe anterior chamber and various structures of the eye involved inaqueous humor drainage (e.g., Schlemm's canal, the sclera, or thesubconjunctival space). See for example, Yu et al. (U.S. Pat. No.6,544,249 and U.S. Pat. Pub. No. 2008/0108933) and Prywes (U.S. Pat. No.6,007,511). Such fluid flow pathways allow for aqueous humor to exit theanterior chamber, thereby reducing IOP.

Such a surgical procedure requires an optical apparatus, such as agoniolens, so that a surgeon may visualize the delivery device withinthe eye and ensure proper placement of the shunt after it has beendeployed from the delivery device.

Further, various manual and automated deployment devices for implantingan intraocular shunt have been described. See, for example, U.S. Pat.No. 6,544,249 and U.S. Pat. Pub. No. 2008/0108933. Most deploymentdevices are coupled to a hollow needle which holds the intraocularshunt. Whether an ab externo approach or an ab interno approach is used,the needle is inserted into the eye to deploy the intraocular shunt intothe eye. The needle is then withdrawn from the eye.

SUMMARY

A problem with treating closed angle glaucoma with surgical interventionis that the closed anterior chamber angle prevents an operator fromadvancing the deployment device into the anterior chamber angle, andthus the device cannot be properly positioned to deploy an intraocularshunt.

The present inventions generally relate, among other things, to methodsfor treating closed angle glaucoma that involve using a deploymentdevice that is configured to both re-open a partially or completelyclosed anterior chamber angle and deploy an intraocular shunt. Byre-opening the anterior chamber angle, the deployment device is providedaccess to the anterior chamber angle so that an operator may properlyposition the device to deploy the intraocular shunt, thereby generatinga fluid flow pathway for outflow of aqueous humor from an anteriorchamber of an eye.

In certain aspects, some methods involve inserting into an eye adeployment device configured to hold an intraocular shunt, using thedevice to re-open an at least partially closed anterior chamber angle ofan eye, and deploying the shunt from the device. Deploying the shuntresults in a flow path from an anterior chamber of the eye to an area oflower pressure. Exemplary areas of lower pressure include intra-Tenon'sspace, the subconjunctival space, the episcleral vein, the subarachnoidspace, the suprachoroidal space, Schlemm's canal, or drainage structuresassociated with the intra-scleral space.

In other aspects, some methods involve inserting into an eye adeployment device configured to hold an intraocular shunt, advancing thedevice such that a protrusion on a distal end of the device advancesinto an at least partially closed anterior chamber angle of the eye,thereby re-opening the closed angle, and deploying the shunt from thedevice. In certain embodiments, a distal portion of the device includesa sleeve and a hollow shaft that is movable within the sleeve.

The present inventions generally provide improved shunts that facilitatedrainage of fluid from an organ. Particularly, some embodiments of theshunt address and solve the problems with intraocular shunts.

The present inventions also generally relate to devices for deployingintraocular shunts from a delivery device without use of an opticalapparatus that contacts the eye, preferably without use of any opticalapparatus. Some devices accomplish shunt deployment without use of anoptical apparatus by having a biased distal portion, such that uponentry of the distal portion of the device into an anterior chamber of aneye, the distal portion slides to fit within the anterior chamber angleof the eye. A resistance feedback feature of the device informs anoperator that the deployment device is properly positioned within theanterior chamber angle of the eye for deployment and proper placement ofthe shunt within the eye.

In particular embodiments, some methods involve inserting into an eye adeployment device configured to hold an intraocular shunt, determiningthat a distal portion of the device is properly positioned within theeye without use of an optical apparatus that contacts the eye, anddeploying the shunt from the device. In certain embodiments, determininginvolves advancing the device until a resistance is encountered. Theresistance indicates to an operator that a distal end of the device hasadvanced across the anterior chamber of the eye and that a distalportion of the device is fitted within an anterior chamber angle of theeye, and is thereby properly positioned for deployment of theintraocular shunt.

Another aspect of some embodiments provides methods for deploying ashunt within an eye including inserting into an eye a deployment deviceconfigured to hold an intraocular shunt, advancing the device until aprotrusion on a distal end of a housing of the device contacts ananterior chamber angle of the eye, thereby providing resistance againstfurther advancement of the device, and deploying the shunt from thedevice. In certain embodiments, a distal portion of the housingcomprises a sleeve and a hollow shaft that is movable within the sleeve.

In certain embodiments, some devices include a housing having an angleddistal end, a deployment mechanism at least partially disposed withinthe housing, and a hollow shaft coupled to the deployment mechanism, inwhich the shaft is configured to hold an intraocular shunt. Some devicesmay further include an intraocular shunt that is at least partiallydisposed within the shaft. In particular embodiments, the angle of thedistal end is substantially identical to an anterior chamber angle of aneye.

The housing of some devices may include a proximal portion and a distalportion. In certain embodiments, the distal portion of the housing ismovable within the proximal portion of the housing. The housing mayfurther include a member that limits axial retraction of the distalportion of the housing.

In certain embodiments, the distal portion includes a capsule and asleeve. In other embodiments, a distal end of the sleeve furtherincludes a protrusion. The protrusion may be formed integrally with thedistal end of the sleeve or may be connected to a distal end of thesleeve. The protrusion may surround the distal end of the sleeve, or theprotrusion may extend around only a portion of the sleeve. In certainembodiments, the protrusion is a collar that surrounds the distal end ofthe sleeve. In other embodiments, the protrusion includes a flat bottomportion and an angled top portion. In particular embodiments, the angleof the top portion is substantially identical to an anterior chamberangle of an eye.

Some methods and devices are typically conducted using an ab internoapproach. Such an approach is contrasted with an ab externo approach,which involves inserting a deployment device through the conjunctiva ofthe eye. Although, some methods may be conducted using an ab externoapproach.

Some methods may be performed such that the distal portion of thedeployment device or shaft is inserted above or below the corneallimbus. Some methods may be performed such that the distal portion ofthe deployment device or shaft is inserted into the eye without removingan anatomical feature of the eye, such as the trabecular meshwork, theiris, the cornea, and the aqueous humor. In certain embodiments, somemethods may be conducted without inducing substantial ocularinflammation such as, for example, subconjunctival blebbing orendophthalmitis.

The deployment configuration involves engagement of the deploymentmechanism. In certain embodiments, the deployment mechanism may includea two stage system. The first stage is a pusher component and the secondstage is a retraction component. Rotation of the deployment mechanismsequentially engages the pusher component and then the retractioncomponent. The pusher component pushes the shunt to partially deploy theshunt from within the shaft, and the retraction component retracts theshaft from around the shunt. The deployment mechanism further includesat least one member that limits axial movement of the shaft.

The hollow shaft of the deployment device may have various shapes andsizes. In certain embodiments, a distal end of the shaft is beveled. Inparticular embodiments, the bevel is a double bevel. In certainembodiments, the angle of the bevel is such that upon insertion of theshaft through the sclera of an eye, the bevel is substantially parallelwith the conjunctiva of an eye. In certain embodiments, the hollow shaftis a needle.

Some devices may be completely automated, partially automated, orcompletely manual. Some devices may be connected to larger roboticsystems or may be used as stand-alone handheld deployment devices. Inparticular embodiments, the device is a handheld device.

Some devices may include an indicator that provides feedback to anoperator as to the state of the deployment mechanism. The indicator maybe any type of indicator known in the art, for example a visualindicator, an audio indicator, or a tactile indicator. In certainembodiments, the indicator is a visual indicator.

Other aspects of some embodiments provide devices for deploying anintraocular shunt that include a housing, in which a distal end of thehousing includes a protrusion, a deployment mechanism at least partiallydisposed within the housing, and a hollow shaft coupled to thedeployment mechanism, in which the shaft is configured to hold anintraocular shunt. The devices may further include an intraocular shuntthat is at least partially disposed within the shaft.

Another aspect of some embodiments provides devices for deploying anintraocular shunt that include a deployment mechanism, a hollow shaftcoupled to the deployment mechanism and configured to hold anintraocular shunt, and a member adapted to provide resistance feedbackto an operator upon a distal portion of the device contacting ananatomical feature of the eye, such as the sclera. The resistancefeedback indicates to an operator that a distal portion of the device isproperly positioned to deploy the shunt.

Another aspect of some embodiments provides devices for deploying anintraocular shunt that include a deployment mechanism, a hollow shaftcoupled to the deployment mechanism and configured to hold anintraocular shunt, and means for providing feedback to an operatoradvancing the shaft. The feedback indicates to an operator that a distalportion of the shaft is properly positioned to deploy the shunt. Incertain embodiments, the feedback is resistance feedback.

Other aspects of some embodiments provide devices for deploying anintraocular shunt including a housing having a proximal portion and adistal portion, in which the distal portion is movable within theproximal portion, a deployment mechanism at least partially disposedwithin the housing, and a hollow shaft coupled to the deploymentmechanism, in which the shaft is configured to hold an intraocularshunt. The devices may further include an intraocular shunt that is atleast partially disposed within the shaft.

Some devices include numerous configurations, such as an insertionconfiguration, a shaft exposure configuration, and a deploymentconfiguration. The insertion configuration includes the hollow shaftfully disposed within the sleeve. The shaft exposure configurationincludes retraction of the capsule to at least partially within theproximal portion of the housing, thereby exposing a distal portion ofthe hollow shaft from the sleeve.

Other aspects of some embodiments provide devices for deploying anintraocular shunt that includes a housing, a deployment mechanism atleast partially disposed within the housing, and a hollow shaft coupledinside the housing to the deployment mechanism, in which the shaft isconfigured to hold an intraocular shunt. These devices include aninsertion configuration and a deployment configuration and the insertionconfiguration involves the shaft being fully disposed within thehousing. The devices may further include an intraocular shunt that is atleast partially disposed within the shaft.

Further, some embodiments relate to eliminating or at least minimizingdamage to the eye of a patient during an intraocular shunt placementprocedure. Intraocular shunts are typically deployed into the eye usinga deployment device that includes or is coupled to a hollow shaft, suchas a needle, that holds the intraocular shunt. The hollow shaft of thedeployment device is inserted into the eye, then the shunt is deployedinto the eye from the deployment device. Once inserted into the eye, theinteraction between the hollow shaft of the deployment device andsurrounding eye tissue oftentimes causes the shaft to become stuck inthe surrounding eye tissue (due to frictional resistance, for example),which can cause severe eye trauma upon shunt deployment or withdrawal ofthe shaft from the eye. This trauma is avoided or at least minimized insome embodiments by loosening the hollow shaft from the surrounding eyetissue prior to deploying the shunt into the eye from the deploymentdevice and/or withdrawing the hollow shaft from the eye.

The present inventions provide improved methods for implantation ofintraocular shunts. In one aspect, some methods involve the insertioninto the eye of a portion of a deployment device comprising anintraocular shunt, loosening the portion of deployment device from thesurrounding eye tissue, deploying the shunt into the eye from thedeployment device, then withdrawing the portion of the deployment devicefrom the eye. In one particular embodiment, the methods involveinserting into the eye a portion of a deployment device comprising anintraocular shunt without removing an anatomical feature of the eye,loosening the portion of the deployment device from the surrounding eyetissue, deploying the shunt into the eye from the deployment device,then withdrawing the portion of the deployment device from the eye.Loosening of the portion of the deployment device inserted into the eyefrom the surrounding eye tissue can be achieved, for example, byrotating the deployment device or a portion of the deployment device,other than the portion inserted into the eye. Rotation of the deploymentdevice, or portion thereof, causes the portion of the deployment deviceinserted into the eye to also rotate, thereby loosening the deploymentdevice from the surrounding eye tissue. Examples of eye tissuesurrounding the portion of the deployment device inserted into the eyeinclude, without limitation, the scleral tissue and/or the trabecularmeshwork.

The loosening and deployment steps of some methods do not have to beconducted in any particular order. For example, some methods may involveinserting into the eye a portion of a deployment device comprising anintraocular shunt, deploying the shunt into the eye from the deploymentdevice, loosening the portion of the deployment device from thesurrounding eye tissue, then withdrawing the portion of the deploymentdevice from the eye.

The deployment device may be configured such that a proximal portion ofthe deployment device is rotated to loosen the portion of the deploymentdevice in the eye from the surrounding eye tissue before or afterdeploying the shunt into the eye. Alternatively, the deployment devicemay be configured such that a distal portion of the deployment device isrotated to loosen the portion of the deployment device in the eye fromthe surrounding eye before or after deploying the shunt into the eye. Inyet another embodiment, the entire deployment device may be rotated toloosen the portion of the deployment device in the eye from thesurrounding eye tissue before or after deploying the shunt into the eye.Preferably, the deployment device, or a portion thereof, is rotatedabout its longitudinal axis. Rotation can be in a clockwise orcounterclockwise direction.

In another aspect, the present inventions relate to methods forimplanting an intraocular shunt into an eye by inserting into the eye aportion of a deployment device comprising an intraocular shunt, wherebyinsertion into the eye is at an angle above or below the corneal limbus,rather than through the corneal limbus. Preferably, the portion of thedeployment device is inserted into the eye at an angle above the corneallimbus. For example, a portion of a deployment device comprising anintraocular shunt is inserted into the eye approximately 1 mm to 2 mmabove the corneal limbus, or any specific value within said range, e.g.,1 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm,1.9 mm or 2 mm above the corneal limbus. The shunt is then deployed intothe eye from the deployment device, and the portion of the deploymentdevice is withdrawn from the eye. Shunt implantation methods above orbelow the corneal limbus are preferably coupled with the step ofloosening the deployment device from the surrounding eye tissue beforeor after deploying the shunt into the eye, as previously described.

Preferably, some methods are conducted using an ab interno approach byinserting a portion of a deployment device comprising an intraocularshunt through the cornea, across the anterior chamber, through thesclera and into an aqueous humor drainage structure such as theintra-Tenon's space, the subconjunctival space, the episcleral vein thesuprachoroidal space or Schlemm's canal. Such an approach is contrastedwith an ab externo approach, which may also be used, and which involvesinserting the portion of the deployment device comprising an intraocularshunt from the outside of the eye through the conjunctiva and inwardthrough the sclera to reach a drainage structure such as Schlemm'scanal. Although, some methods may be conducted using an ab externoapproach.

In other certain embodiments, some methods are conducted without the useof an optical apparatus, particularly an optical apparatus that directlycontacts the eye, such as a goniolens. In yet other certain embodiments,some methods are conducted using an optical apparatus that does notdirectly contact the eye, such as an ophthalmic microscope.

In a particular embodiment, some methods are reversible. That is,intraocular shunts that are implanted into the eye in accordance withsome methods can be removed from the eye and a second shunt can beimplanted in the eye.

Deployment of an intraocular shunt into the eye in accordance with somemethods results in the formation of a passage that directs aqueous humorfluid flow from an area of high pressure in the eye, typically theanterior chamber, to an area of lower pressure within the eye, such asthe intra-Tenon's space, the subconjunctival space, the episcleral vein,the suprachoroidal space or Schlemm's canal. Alternatively, the shunt isdeployed in accordance with some methods such that it form a passagethat directs aqueous humor fluid flow from an area of high pressure,such as the anterior chamber, to an area of lower pressure within thehead, such as the subarachnoid space. In a preferred embodiment,deployment of an intraocular shunt in accordance with some methodsresults in the formation of a passage that directs aqueous humor fluidflow from the anterior chamber of the eye to the intra-Tenon's space.

The present inventions generally relate to methods for deployingintraocular shunts into the subconjunctival space the eye while avoidingor minimizing contact with the conjunctiva. In particular, the presentinventions provide methods for deploying an intraocular shunt into theeye such that the shunt forms a drainage pathway from the anteriorchamber of the eye to the region of the eye that is bound between thesclera and Tenon's capsule, referred to herein as the intra-Tenon'sspace. Deployment of an intraocular shunt such that the shunt inlet(i.e., the portion of the shunt that receives fluid from an anteriorchamber of the eye) terminates in the anterior chamber and the shuntoutlet (i.e., the portion of the shunt that directs fluid to theintra-Tenon's space) terminates in the intra-Tenon's space safeguardsthe integrity of the conjunctiva to allow subconjunctival drainagepathways to successfully form.

Some methods involve inserting into the eye a hollow shaft that isconfigured to hold an intraocular shunt, deploying the shunt from theshaft such that the shunt forms a passage from the anterior chamber tothe intra-Tenon's space, and withdrawing the hollow shaft from the eye.The hollow shaft may hold the shunt within the interior of hollow shaft.Alternatively, the hollow shaft may hold the shunt on an outer surfaceof the shaft. In certain embodiments, some methods involve the use of ahollow shaft configured to hold an intraocular shunt, as previouslydescribed, wherein a portion of the hollow shaft extends linearly alonga longitudinal axis and at least one other portion of the shaft extendsoff the longitudinal axis, to insert and deploy the intraocular shuntinto the eye such that the shunt forms a passage from the anteriorchamber to the intra-Tenon's space.

Optionally, an aqueous fluid is injected into the eye simultaneouslywith or prior to the insertion and deployment steps of some methods. Forexample, an aqueous solution may be injected below Tenon's capsule toballoon the capsule away from the sclera and allow positioning of theintraocular shunt in the intra-Tenon's space.

In certain aspects, the present inventions generally provide shuntscomposed of a material that has an elasticity modulus that is compatiblewith an elasticity modulus of tissue surrounding the shunt. In thismanner, some embodiments of the shunt are flexibility matched with thesurrounding tissue, and thus will remain in place after implantationwithout the need for any type of anchor that interacts with thesurrounding tissue. Consequently, some embodiments of the shunt willmaintain fluid flow away for an anterior chamber of the eye afterimplantation without causing irritation or inflammation to the tissuesurrounding the eye.

Although discussed in the context of the eye, the elasticity modulus ofthe shunt may be matched to the elasticity modulus of any tissue. Thus,some embodiments of the shunt may be used to drain fluid from any organ.In particular embodiments, the organ is an eye. Some embodiments of theshunt may define a flow path from an area of high pressure in the eye(e.g., an anterior chamber) to an area of lower pressure in the eye(e.g., intra-Tenon's space, the subconjunctival space, the episcleralvein, the suprachoroidal space, and Schlemm's canal).

In other aspects, the present inventions generally provide shunts inwhich a portion of the shunt is composed of a flexible material that isreactive to pressure, i.e., an inner diameter of the shunt fluctuatesdepending upon the pressures exerted on that portion of the shunt. Thus,the flexible portion of the shunt acts as a valve that regulates fluidflow through the shunt. After implantation, intraocular shunts havepressure exerted upon them by tissues surrounding the shunt (e.g.,scleral tissue) and pressure exerted upon them by aqueous humor flowingthrough the shunt. When the pressure exerted on the flexible portion ofthe shunt by the surrounding tissue is greater than the pressure exertedon the flexible portion of the shunt by the fluid flowing through theshunt, the flexible portion decreases in diameter, restricting flowthrough the shunt. The restricted flow results in aqueous humor leavingthe anterior chamber at a reduced rate.

When the pressure exerted on the flexible portion of the shunt by thefluid flowing through the shunt is greater than the pressure exerted onthe flexible portion of the shunt by the surrounding tissue, theflexible portion increases in diameter, increasing flow through theshunt. The increased flow results in aqueous humor leaving the anteriorchamber at an increased rate.

The flexible portion of the shunt may be any portion of the shunt. Incertain embodiments, the flexible portion is a distal portion of theshunt. In certain embodiments, the entire shunt is composed of theflexible material.

Other aspects of the present inventions generally provide multi-portshunts. Such shunts reduce probability of the shunt clogging afterimplantation because fluid can enter or exit the shunt even if one ormore ports of the shunt become clogged with particulate. In certainembodiments, the shunt includes a hollow body defining a flow path andmore than two ports, in which the body is configured such that aproximal portion receives fluid from the anterior chamber of an eye anda distal portion directs the fluid to a location of lower pressure withrespect to the anterior chamber.

The shunt may have many different configurations. In certainembodiments, the proximal portion of the shunt (i.e., the portiondisposed within the anterior chamber of the eye) includes more than oneport and the distal portion of the shunt (i.e., the portion that islocated in an area of lower pressure with respect to the anteriorchamber such as intra-Tenon's space, the subconjunctival space, theepiscleral vein, the suprachoroidal space, or Schlemm's canal) includesa single port. In other embodiments, the proximal portion includes asingle port and the distal portion includes more than one port. In stillother embodiments, the proximal and the distal portions include morethan one port.

The ports may be positioned in various different orientations and alongvarious different portions of the shunt. In certain embodiments, atleast one of the ports is oriented at an angle to the length of thebody. In certain embodiments, at least one of the ports is oriented 90°to the length of the body.

The ports may have the same or different inner diameters. In certainembodiments, at least one of the ports has an inner diameter that isdifferent from the inner diameters of the other ports.

Other aspects of the present inventions generally provide shunts withoverflow ports. Those shunts are configured such that the overflow portremains closed until there is a pressure build-up within the shuntsufficient to force open the overflow port. Such pressure build-uptypically results from particulate partially or fully clogging an entryor an exit port of the shunt. Such shunts reduce probability of theshunt clogging after implantation because fluid can enter or exit theshunt by the overflow port even if one port of the shunt becomes cloggedwith particulate.

In certain embodiments, the shunt includes a hollow body defining aninlet configured to receive fluid from an anterior chamber of the eyeand an outlet configured to direct the fluid to a location of lowerpressure with respect to the anterior chamber, the body furtherincluding at least one slit. The slit may be located at any place alongthe body of the shunt. In certain embodiments, the slit is located inproximity to the inlet. In other embodiments, the slit is located inproximity to the outlet. In certain embodiments, there is a slit inproximity to both the inlet and the outlet of the shunt.

In certain embodiments, the slit has a width that is substantially thesame or less than an inner diameter of the inlet. In other embodiments,the slit has a width that is substantially the same or less than aninner diameter of the outlet. Generally, the slit does not direct thefluid unless the outlet is obstructed. However, the shunt may beconfigured such that the slit does direct at least some of the fluideven if the inlet or outlet is not obstructed.

In other aspects, the present inventions generally provide a shunthaving a variable inner diameter. In particular embodiments, thediameter increases from inlet to outlet of the shunt. By having avariable inner diameter that increases from inlet to outlet, a pressuregradient is produced and particulate that may otherwise clog the inletof the shunt is forced through the inlet due to the pressure gradient.Further, the particulate will flow out of the shunt because the diameteronly increases after the inlet.

In certain embodiments, the shunt includes a hollow body defining a flowpath and having an inlet configured to receive fluid from an anteriorchamber of an eye and an outlet configured to direct the fluid to alocation of lower pressure with respect to the anterior chamber, inwhich the body further includes a variable inner diameter that increasesalong the length of the body from the inlet to the outlet. In certainembodiments, the inner diameter continuously increases along the lengthof the body. In other embodiments, the inner diameter remains constantalong portions of the length of the body. Exemplary locations of lowerpressure include the intra-Tenon's space, the subconjunctival space, theepiscleral vein, the subarachnoid space, and Schlemm's canal.

In certain embodiments, some embodiments of the shunt may be coated orimpregnated with at least one pharmaceutical and/or biological agent ora combination thereof. The pharmaceutical and/or biological agent maycoat or impregnate an entire exterior of the shunt, an entire interiorof the shunt, or both. Alternatively, the pharmaceutical and/orbiological agent may coat and/or impregnate a portion of an exterior ofthe shunt, a portion of an interior of the shunt, or both. Methods ofcoating and/or impregnating an intraocular shunt with a pharmaceuticaland/or biological agent are known in the art. See, for example,Darouiche (U.S. Pat. Nos. 7,790,183; 6,719,991; 6,558,686; 6,162,487;5,902,283; 5,853,745; and 5,624,704) and Yu et al. (U.S. Pat. Pub. No.2008/0108933). The content of each of these references is incorporatedby reference herein its entirety.

In certain embodiments, the exterior portion of the shunt that residesin the anterior chamber after implantation (e.g., about 1 mm of theproximal end of the shunt) is coated and/or impregnated with thepharmaceutical or biological agent. In other embodiments, the exteriorof the shunt that resides in the scleral tissue after implantation ofthe shunt is coated and/or impregnated with the pharmaceutical orbiological agent. In other embodiments, the exterior portion of theshunt that resides in the area of lower pressure (e.g., theintra-Tenon's space or the subconjunctival space) after implantation iscoated and/or impregnated with the pharmaceutical or biological agent.In embodiments in which the pharmaceutical or biological agent coatsand/or impregnates the interior of the shunt, the agent may be flushedthrough the shunt and into the area of lower pressure (e.g., theintra-Tenon's space or the subconjunctival space).

Any pharmaceutical and/or biological agent or combination thereof may beused with some embodiments of the shunt. The pharmaceutical and/orbiological agent may be released over a short period of time (e.g.,seconds) or may be released over longer periods of time (e.g., days,weeks, months, or even years). Exemplary agents include anti-mitoticpharmaceuticals such as Mitomycin-C or 5-Fluorouracil, anti-VEGF (suchas Lucintes, Macugen, Avastin, VEGF or steroids).

The shunts discussed above and herein are described relative to the eyeand, more particularly, in the context of treating glaucoma and solvingthe above identified problems relating to intraocular shunts.Nonetheless, it will be appreciated that shunts described herein mayfind application in any treatment of a body organ requiring drainage ofa fluid from the organ and are not limited to the eye.

The present inventions provide devices and methods for self-guidedimplantation of soft gel tissue compliant intraocular shunts in thesuprachoroidal space. Shunt placement in the suprachoroidal space avoidscontact with the conjunctiva, thus safeguarding the integrity of theconjunctiva. Implanting shunts made of soft, tissue compliant materialavoid the creation of a cyclodialysis cleft and reduces or eliminatesthe risk of hypotony and related side effects.

Some embodiments of the device accomplish self-guided shunt deploymentin the suprachoroidal space by having a flexible hollow shaft with abend that biases the shunt to follow the scleral spur as it is deployedfrom the shaft. The hollow shaft is pre-bent to match the angle or arcof the sclera. In a pre-deployment configuration, the shaft is disposedwithin the device. The rigidity of the device holds the hollow shaft ina straight configuration. Upon its exposure from the device, the hollowshaft reverts to its pre-bent configuration. Such a pre-bend allows thehollow shaft to follow the scleral spur down along the sclera in aself-guided manner to the suprachoroidal space. Additionally, theflexibility of the hollow shaft allows it to continually bend and flexin response to the anatomy as the hollow shaft advances from the device.Once properly positioned, the shunt is deployed from the shaft. The bendin the shaft self-guides the shunt along the scleral spur of the eye asthe shaft is retracted into the device and the shunt is deployed fromthe shaft.

In certain aspects, some embodiments of the device also include ahousing and a deployment mechanism at least partially disposed in thehousing. In certain embodiments, the hollow shaft is coupled to thedeployment mechanism. The housing may include two components, a proximalportion and a distal portion. The components are configured such thatthe distal portion is movable within the proximal portion. In certainembodiments, the distal portion of the housing includes a stiff sleeveand the shaft is movably disposed within the sleeve. In otherembodiments, the distal portion is without a stiff outer sleeve. Aspreviously described, the shaft is flexible and pre-bent to match anangle of the sclera. In certain embodiments, the distal end of thehollow shaft includes a sharp tip to assist in piercing the sclera. Incertain embodiments, the hollow shaft is a flexible needle.

In other embodiments, a distal end of the sleeve further includes aprotrusion. The protrusion may be formed integrally with the distal endof the sleeve or may be connected to a distal end of the sleeve. Theprotrusion may surround the distal end of the sleeve, or the protrusionmay extend around only a portion of the sleeve. In certain embodiments,the protrusion is a collar that surrounds the distal end of the sleeve.In other embodiments, the protrusion includes a flat bottom portion andan angled top portion. In particular embodiments, the angle of the topportion is substantially identical to an anterior chamber angle of aneye.

Other aspects of some embodiments provide for methods of using the abovedescribed devices for inserting a intraocular shunt into thesuprachoroidal space of an eye. Such methods involve inserting the abovedevice into an eye and deploying a shunt from the device within the eyesuch that a proximal portion of the shunt receives fluid from ananterior chamber of an eye and a distal portion of the shunt directs thefluid to the suprachoroidal space. Some methods may also involveinjecting a drug into the suprachoroidal space prior to deploying theshunt from the device. Exemplary drugs include drug is a BSS/steroids orantifibrotic agents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides a cross-sectional diagram of the general anatomy of theeye.

FIG. 2 provides another cross-sectional view the eye, and certainanatomical structures of the eye.

FIG. 3 depicts, implantation of an intraocular shunt with a distal endof a deployment device holding a shunt, shown in cross-section.

FIGS. 4A-4B depict a deployment device having a plunger type mechanismfor deploying an intraocular shunt into the eye.

FIG. 5 depicts an example of a deployment device configured to hold anintraocular shunt.

FIG. 6A depicts a hollow shaft having a bend in a distal portion of theshaft.

FIG. 6B depicts a hollow shaft having a U-shape.

FIG. 6C depicts a hollow shaft having a V-shape.

FIG. 7A depicts a simulation of the exit site distance from the limbusand height above the iris after needle entry at the limbus using an abinterno procedure.

FIG. 7B depicts a simulation of the exit site distance from the limbusand height above the iris after needle entry above the limbus using anab interno procedure.

FIGS. 8 and 9 show an intraocular shunt deployed within the eye. Aproximal portion of the shunt resides within the intra-Tenon's space. Amiddle portion of the shunt resides in the sclera.

FIG. 10A depicts the tip bevel portion of a triple-ground needle tip.

FIG. 10B depicts the flat bevel portion of a triple-ground needle tip.

FIG. 10C depicts an intraocular shunt within a triple-ground needle tip.

FIG. 10D depicts 100% penetration of the flat bevel portion of atriple-ground needle tip through the sclera of an eye.

FIG. 11A depicts an intraocular shunt inserted into the scleral channelusing a beveled needle tip to completely penetrate the scleral tissueprior to insertion of the shunt.

FIG. 11B depicts an intraocular shunt inserted into the scleral channelusing a beveled needle tip to partially penetrate the scleral tissueprior to insertion of the shunt.

FIG. 12 provides a schematic of a shunt having a flexible portion.

FIGS. 13A-13C provide schematics of a shunt implanted into an eye forregulation of fluid flow from the anterior chamber of the eye to adrainage structure of the eye.

FIGS. 14A-14C show different embodiments of multi-port shunts. FIG. 14Ashows an embodiment of a shunt in which the proximal portion of theshunt includes more than one port and the distal portion of the shuntincludes a single port.

FIG. 14B shows another embodiment of a shunt in which the proximalportion includes a single port and the distal portion includes more thanone port.

FIG. 14C shows another embodiment of a shunt in which the proximalportions include more than one port and the distal portions include morethan one port.

FIGS. 15A and 15B show different embodiments of multi-port shunts havingdifferent diameter ports.

FIGS. 16A-16C provide schematics of shunts having a slit located along aportion of the length of the shunt.

FIG. 17 depicts a shunt having multiple slits along a length of theshunt.

FIG. 18 depicts a shunt having a slit at a proximal end of the shunt.

FIGS. 19A and 19B show schematics of shunt that have a variable innerdiameter.

FIGS. 20A-20D depict a shunt having multiple prongs at a distal and/orproximal end.

FIGS. 21A-21D depict a shunt having a longitudinal slit at a distaland/or proximal end.

FIG. 22A is a schematic showing an embodiment of a shunt deploymentdevice according to some embodiments.

FIG. 22B shows a cross sectional view of the device of FIG. 22A. In thisfigure, the distal portion of the housing is extended from the proximalportion of the housing.

FIG. 22C shows a cross sectional view of the device of FIG. 22A. In thisfigure, the distal portion of the housing is retracted within theproximal portion of the housing.

FIG. 22D shows another cross sectional view of an embodiment of thedevice of FIG. 22A.

FIG. 22E is a schematic showing an enlarged view of a protrusion on adistal end of a distal portion of a housing of the device of FIG. 22A.In this figure, a bottom portion of the protrusion is flat and a topportion of the protrusion is angled.

FIGS. 23A-23C are schematics showing an enlarged view of a protrusion ona distal end of a distal portion of a housing of some embodiments of thedevice.

FIG. 23B is a side view of the protrusion shown in FIG. 23A.

FIG. 23C is a top view of the protrusion shown in FIG. 23A.

FIG. 24A shows a deployment device in an insertion configuration and fitinto an anterior chamber of an eye.

FIG. 24B shows a deployment device in an insertion configuration andinserted at too shallow an angled, thus abutting the sclera above theanterior chamber angle.

FIG. 24C shows a deployment device in an insertion configuration afterthe protrusion has caused the device to slide down the sclera and be fitinto an anterior chamber of an eye.

FIG. 24D shows a deployment device in an insertion configuration andinserted at too steep an angled, thus abutting the iris below theanterior chamber angle.

FIG. 24E shows a deployment device in an insertion configuration afterthe protrusion has caused the device to deflect off of the iris andslide along the iris and be fit into an anterior chamber of an eye.

FIG. 25 is a schematic showing an embodiment of a shunt deploymentdevice according to some embodiments.

FIG. 26 shows an exploded view of the device shown in FIG. 25.

FIGS. 27A-27D are schematics showing different enlarged views of thedeployment mechanism of the deployment device with the shaft in astraight configuration, as if the shaft is within the stiff outersleeve.

FIGS. 28A-28C are schematics showing interaction of the deploymentmechanism with a portion of the housing of the deployment device.

FIG. 28C shows the shaft in a straight configuration, as if it is withinthe stiff outer sleeve.

FIG. 29 depicts a schematic of an exemplary intraocular shunt.

FIG. 30 shows a cross sectional view of the deployment mechanism of thedeployment device with the shaft in a straight configuration, as if theshaft is within the stiff outer sleeve.

FIG. 31A is a schematic showing deployment some embodiments of thedevice in a pre-deployment or insertion configuration.

FIG. 31B shows an enlarged view of the distal portion of the deploymentdevice of FIG. 31A. This figure shows an intraocular shunt loaded withina hollow shaft of the deployment device and that the shaft is completelydisposed within the sleeve of the housing. In this configuration, thehollow shaft is straight.

FIG. 31C show a schematic of the deployment mechanism in apre-deployment or insertion configuration.

FIG. 31D is another schematic showing deployment some embodiments of thedevice in a pre-deployment or insertion configuration.

FIGS. 32A-32B are schematics showing insertion of a device into ananterior chamber of the eye, according to some embodiments. FIG. 32A isa magnified view of the position of the distal portion of the devicerelative to the proximal portion of the device in the insertionconfiguration. FIG. 32B is a magnified view of the sleeve of the deviceinserted into the eye. This figure also shows the sleeve and protrusionfitted within an anterior chamber angle of the eye.

FIG. 33A is a schematic showing extension of the shaft from within thesleeve, which is accomplished by partial retraction of the distalportion of housing to within the proximal portion of housing.

FIG. 33B is a magnified view of the sleeve of the device inserted intothe eye, following a procedure as shown in FIG. 33A.

FIGS. 34A-34B show schematics of the deployment mechanism at the end ofthe first stage of deployment of the shunt from the deployment devicewith the shaft in a straight configuration, as if the shaft is withinthe stiff outer sleeve.

FIG. 34C shows an enlarged view of the distal portion of the deploymentdevice of FIG. 34A. This figure shows an intraocular shunt partiallydeployed from within a hollow shaft of the deployment device.

FIG. 34D shows an enlarged view of the distal portion of the deploymentdevice of FIG. 34A, in which the shaft is shown exposed from the sleeveand is in a bent configuration. This figure shows an intraocular shuntpartially deployed from within a hollow shaft of the deployment device.

FIG. 35A-35B are schematics showing the deployment device aftercompletion of the first stage of deployment of the shunt from the deviceand in to the eye. FIG. 35A is a magnified view of the position of thedistal portion of the device relative to the proximal portion of thedevice. FIG. 35B is a magnified view of the sleeve of the deviceinserted into the eye and the shaft extended from the sleeve.

FIG. 36A show a schematic of the deployment mechanism at the end of thesecond stage of deployment.

FIG. 36B shows another schematic of the deployment device at the end ofthe second stage of deployment.

FIG. 36C is a magnified view of the sleeve of the device inserted intothe eye, retraction of the shaft into the sleeve, and the shunt beingdeployed from the sleeve.

FIG. 36D shows another view of the deployment device at the end of thesecond stage of deployment.

FIG. 37A is a schematic showing the deployment device after completionof deployment of the shunt from the device and in to the eye.

FIG. 37B is a magnified view of the sleeve of the device being removedfrom the eye.

FIGS. 38A-38E show an intraocular shunt being deployed within the eye,according to another embodiment.

DETAILED DESCRIPTION

The present inventions generally relate to methods for treating closedangle glaucoma that involve using a deployment device that is configuredto both re-open a partially or completely closed anterior chamber angleand deploy an intraocular shunt. In certain aspects, some methodsinvolve inserting into an eye a deployment device configured to hold anintraocular shunt, using the device to re-open an at least partiallyclosed anterior chamber angle of an eye, and deploying the shunt fromthe device.

FIG. 1 provides a schematic diagram of the general anatomy of the eye.An anterior aspect of the anterior chamber 1 of the eye is the cornea 2,and a posterior aspect of the anterior chamber 1 of the eye is the iris4. Beneath the iris 4 is the lens 5. The anterior chamber 1 is filledwith aqueous humor 3. The aqueous humor 3 drains into a space(s) 6 belowthe conjunctiva 7 through the trabecular meshwork (not shown in detail)of the sclera 8. The aqueous humor is drained from the space(s) 6 belowthe conjunctiva 7 through a venous drainage system (not shown).

FIG. 2 provides a cross-sectional view of a portion of the eye, andprovides greater detail regarding certain anatomical structures of theeye. In particular, FIG. 2 shows the relationship of the conjunctiva 12and Tenon's capsule 13. Tenon's capsule 13 is a fascial layer ofconnective tissue surrounding the globe and extra-ocular muscles. Asshown in FIG. 2, it is attached anteriorly to the limbus of the eye andextends posteriorly over the surface of the globe until it fuses withthe dura surrounding the optic nerve. In FIG. 2, number 9 denotes thelimbal fusion of the conjunctiva 12 and Tenon's capsule 13 to the sclera11. The conjunctiva 12 and Tenon's capsule 13 are separate membranesthat start at the limbal fusion 9 and connect to tissue at the posteriorof the eye. The space formed below the conjunctiva 12 is referred to asthe subconjunctival space, denoted as number 14. Below Tenon's capsule13 there are Tenon's adhesions that connect the Tenon's capsule 13 tothe sclera 11. The space between Tenon's capsule 13 and the sclera 11where the Tenon's adhesions connect the Tenon's capsule 13 to the sclera11 is referred to as the intra-Tenon's space, denoted as number 10.

In conditions of glaucoma, the pressure of the aqueous humor in the eye(anterior chamber) increases and this resultant increase of pressure cancause damage to the vascular system at the back of the eye andespecially to the optic nerve. The treatment of glaucoma and otherdiseases that lead to elevated pressure in the anterior chamber involvesrelieving pressure within the anterior chamber to a normal level.

Glaucoma filtration surgery is a surgical procedure typically used totreat glaucoma. The procedure involves placing a shunt in the eye torelieve intraocular pressure by creating a pathway for draining aqueoushumor from the anterior chamber of the eye. The shunt is typicallypositioned in the eye such that it creates a fluid-flow pathway betweenthe anterior chamber of the eye and a region of lower pressure. Variousstructures and/or regions of the eye having lower pressure that havebeen targeted for aqueous humor drainage include Schlemm's canal, thesubconjunctival space, the episcleral vein, the suprachoroidal space, orthe subarachnoid space. Methods of implanting intraocular shunts areknown in the art. Shunts may be implanted using an ab externo approach(entering through the conjunctiva and inwards through the sclera) or anab interno approach (entering through the cornea, across the anteriorchamber, and through the trabecular meshwork and sclera).

Ab interno approaches for implanting an intraocular shunts have beendescribed and may vary depending on the structure targeted for aqueoushumor drainage. For example, ab interno approaches for implanting anintraocular shunt into the subconjunctival space are shown in Yu et al.(U.S. Pat. No. 6,544,249 and U.S. Pat. Pub. No. 2008/0108933) and Prywes(U.S. Pat. No. 6,007,511), the contents of each of which areincorporated by reference herein in its entirety. Briefly and withreference to FIG. 3, a surgical intervention to implant the shuntinvolves inserting into the eye a portion of a deployment that holds anintraocular shunt, and deploying the shunt within the eye 16. Theportion of the deployment device 15 holding the shunt enters the eye 16through the cornea 17 (ab interno approach). The portion of thedeployment device 15 is advanced across the anterior chamber 20 (asdepicted by the broken line) in what is referred to as a transpupilimplant insertion. The portion of the deployment device 15 is advancedthrough the sclera 21 until a distal portion of the device is inproximity to the subconjunctival space. The shunt is then deployed fromthe deployment device, producing a conduit between the anterior chamberand the subconjunctival space to allow aqueous humor to drain throughthe conjunctival lymphatic system.

Previously proposed deployment devices for implanting an intraocularshunt into the eye, whether using an ab externo procedure or an abinterno procedure, typically include a plunger-type mechanism fordeploying the shunt into the eye, such as the deployment deviceillustrated in FIG. 3. The deployment device in FIG. 3 is shown largerin FIG. 4A, and the distal portion of the deployment device is shownmagnified in FIG. 4B. As shown in FIGS. 4A and 4B, the deployment deviceincludes an assembly 20 that includes a hollow shaft 22 defining aninner chamber 24. Placed within the inner chamber 24 of the hollow shaft22 is a cylindrical inner tube or plunger 32 that is coaxial with theshaft 22. In the loaded and ready to use condition, the intraocularshunt 26 is also placed or otherwise disposed within the hollow innerchamber 24 of the shaft 22 and is distally located relative to plunger32. Both the intraocular shunt 26 and plunger 32 may be placed over andsupported by optional guidewire 28. The intraocular shunt is deployedinto the eye by advancing the plunger to push the intraocular shunt fromthe shaft into the eye. The shaft is then withdrawn from the eye.

However, complications can arise when using such deployment devices dueto the frictional interaction between the deployment device and thesurrounding eye tissue that results upon insertion of the deploymentdevice into the eye and/or deployment of the intraocular shunt into theeye from the deployment device. Moderate to severe eye trauma can occur,beyond any trauma due to insertion of the deployment device, if theportion of the deployment device inserted into the eye is not loosenedbefore or after deployment of the intraocular shunt from the device andprior to withdrawing the portion of the deployment device from the eye.

The present inventions provide improved methods for implanting anintraocular shunt into the eye while avoiding or at least minimizing theamount of trauma to the eye that is typically involved with shuntimplantation procedures. According to some methods, any frictionalresistance between the deployment device and surrounding eye tissue thatis created upon insertion of a portion of a deployment device in the eyeis resolved by loosening the portion of the deployment device from thesurrounding eye tissue before or after deployment of the intraocularshunt from the device and prior to withdrawing the portion of thedeployment device from the eye. The methods can be used in conjunctionwith any known shunt deployment device, and in particular, anydeployment device that includes a portion for holding an intraocularshunt or is coupled to a hollow shaft which is configured to hold anintraocular shunt.

Preferably, at least a portion of the deployment device is rotatedbefore the shunt is deployed into the eye from the deployment device, inorder to loosen the portion of the device inserted into the eye from thesurrounding eye tissue prior to withdrawing the deployment device fromthe eye. Rotation may be clockwise or counterclockwise, and may beperformed manually or in an automated manner. Rotation of only a distalportion of the deployment device may be sufficient to loosen the portionof the deployment device in the eye from the surrounding eye tissue,depending on the configuration of the device. Alternatively, rotation ofthe entire deployment device serves to loosen the portion of thedeployment device in the eye from the surrounding eye tissue. Rotationof the deployment device, or a portion thereof, causes the portion ofthe deployment device that is inserted into the eye to also rotate,thereby loosening the portion of the deployment device in the eye formthe surrounding eye tissue. Examples of surrounding eye tissue includebut are not limited to the scleral tissue and the trabecular meshwork.

The deployment device, or a portion thereof, is rotated clockwise orcounterclockwise about the longitudinal axis of the deployment deviceitself. The rotation about the longitudinal axis is preferably between1° and 360°, or any specific value within said range, e.g., 1°, 3°, 5°,10°, 15°, 30°, 45°, 60°, 75°, 90°, 105°, 120°, 135°, 150° 165°, 180°,195°, 210°, 225°, 240°, 255°, 270°, 285°, 300°, 315°, 330°, 345° or360°.

As previously stated, some methods can be used in conjunction with anyshunt deployment device. FIG. 5 provides an exemplary schematic of ahollow shaft for use in conjunction with a deployment device inaccordance with some methods. This shows hollow shaft 22 that isconfigured to hold an intraocular shunt 23. The shaft may hold the shuntwithin the hollow interior 24 of the shaft 22. Alternatively, the hollowshaft may hold the shunt on an outer surface 25 of the shaft 22. Inparticular embodiments, the shunt is held within the hollow interior 24of the shaft 22. Generally, in one embodiment, the intraocular shuntsare of a cylindrical shape and have an outside cylindrical wall and ahollow interior. The shunt may have an inside diameter of approximately10-250 microns, an outside diameter of approximately 190-300 microns,and a length of approximately 0.5 mm to 20 mm, such as, for example, 6mm to 14 mm. The hollow shaft 22 is configured to at least hold a shuntof such shape and such dimensions. However, the hollow shaft 22 may beconfigured to hold shunts of different shapes and different dimensionsthan those described above, and some embodiments encompass a shaft 22that may be configured to hold any shaped or dimensioned intraocularshunt.

In some embodiments, the hollow shaft for use in accordance with somemethods is straight along the entire length of the shaft. Alternatively,a portion of the hollow shaft extends linearly along a longitudinal axisand at least one other portion of the shaft extends off the longitudinalaxis. For example, the hollow shaft may have a bend in the distalportion of the shaft, a U-shape, or an arcuate or V-shape in at least aportion of the shaft. Examples of such hollow shafts suitable for usewith some methods include but are not limited to the hollow shaftsdepicted in FIGS. 6A-6C.

Preferably, some methods are conducted by making an incision in the eyeprior to insertion of the deployment device configured to hold theintraocular shunt. Although in particular embodiments, some methods maybe conducted without making an incision in the eye prior to insertion ofthe deployment device configured to hold the intraocular shunt. Incertain embodiments, the distal end of the deployment device (i.e. theportion that is inserted into the eye) has a sharpened point or tip. Forexample, the distal end of the deployment device includes or is coupledto a needle configured to hold an intraocular shunt. Needles that areconfigured to hold an intraocular shunt are commercially available fromTerumo Medical Corp. (Elkington Md.). In a particular embodiment, thedistal end of the deployment device is coupled to a needle having ahollow interior and a beveled tip, and the intraocular shunt is heldwithin the hollow interior of the needle. In another particularembodiment, the distal end of the deployment device is coupled to aneedle having a hollow interior and a triple ground point or tip.

Some methods are preferably conducted without needing to remove ananatomical portion or feature of the eye, including but not limited tothe trabecular meshwork, the iris, the cornea, or aqueous humor. Somemethods are also preferably conducting without inducing substantialocular inflammation, such as subconjunctival blebbing orendophthalmitis. Such methods are preferably achieved using an abinterno approach by inserting the deployment device comprising theintraocular shunt through the cornea, across the anterior chamber,through the trabecular meshwork and sclera and into a drainage structuresuch as Schlemm's canal, the subconjunctival space, the episcleral vein,the suprachoroidal space, the intra-Tenon's space or the subarachnoidspace. However, some methods may be conducted using an ab externoapproach.

When some methods are conducted using an ab interno approach, thedeployment device is preferably inserted into the eye at an angle aboveor below the corneal limbus, inserted in contrast with entering throughthe corneal limbus. Preferably, the deployment device is inserted abovethe corneal limbus. For example, the deployment device is insertedapproximately 0.25 to 3.0 mm, preferably approximately 0.5 to 2.5 mm,more preferably approximately 1.0 mm to 2.0 mm above the corneal limbus,or any specific value within said ranges, e.g., approximately 1.0 mm,approximately 1.1 mm, approximately 1.2 mm, approximately 1.3 mm,approximately 1.4 mm, approximately 1.5 mm, approximately 1.6 mm,approximately 1.7 mm, approximately 1.8 mm, approximately 1.9 mm orapproximately 2.0 mm above the corneal limbus.

Entering at an angle above or below the corneal limbus is advantageousfor placing the shunt farther from the limbus at the exit site. It alsoadds more distance between the shunt and the iris. FIG. 7A demonstratesthe change in location of the shunt sclera exit and the height above theiris in the chamber at different angles of entry using a hollow needleconfigured to hold an intraocular shunt.

Without intending to be bound by any theory, placement of the shuntfarther from the limbus at the exit site, as provided by an angle ofentry above the limbus, is believed to provide access to more lymphaticchannels for drainage of aqueous humor, such as the episcleral lymphaticnetwork, in addition to the conjunctival lymphatic system. A higherangle of entry also results in flatter placement in the intra-Tenon'sspace so that there is less bending of the shunt, less pressure onTenon's capsule, and subsequently less erosion pressure on theconjunctiva via Tenon's capsule.

For example, as shown in FIG. 7A, shaft entry at the limbus 52 resultsin exit site distance 53 of approximately 1.6 mm from the limbus, andvery close proximity to the iris 4. Such placement results in a largedegree of bending of the shunt, resulting in increased pressure onTenon's capsule and subsequently on the conjunctiva. In contrast, a highangle of entry 54 above the limbus 52 (e.g., 2 mm above the limbus 52),results in an exit site distance 53 of approximately 2.1 mm from thelimbus and a height well above the iris 4, as shown in FIG. 7B. Suchplacement results in flatter placement in the intra-Tenon's space sothat there is less bending of the shunt, less pressure on Tenon'scapsule, and subsequently less erosion pressure on the conjunctiva viaTenon's capsule.

Deployment of an intraocular shunt in the eye in accordance with somemethods results in the formation of a passage that directs fluid flowfrom an area of high pressure in the eye, typically the anteriorchamber, to an area of lower pressure within the eye or within the head,to relieve or reduce intraocular pressure. Areas of lower pressurewithin the eye that are suited for aqueous humor drainage include butare not limited to the intra-Tenon's space, the subconjunctival space,the episceleral vein, the suprachoroidal space and Schlemm's canal.Alternatively, the subarachnoid space may provide a drainage outlet foraqueous humor from the anterior chamber. Preferably, deployment of theshunt results in the formation of a passage for directing fluid flowbetween the anterior chamber and the intra-Tenon's space.

Deployment of an intraocular shunt such that the inlet (i.e., theportion of the shunt that receives fluid from an anterior chamber of theeye) terminates in the anterior chamber and the outlet (i.e., theportion of the shunt that directs fluid to the intra-Tenon's space)terminates in the intra-Tenon's space provides superior benefits overdeployment generally in the subconjunctival space. Deployment of theshunt outlet in the intra-Tenon's space safeguards the integrity of theconjunctiva to allow subconjunctival drainage pathways to successfullyform. See, for example, Yu et al., Progress in Retinal and Eye Research,28: 303-328 (2009)). Additionally, drainage into the intra-Tenon's spaceprovides access to more lymphatic channels than just the conjunctivallymphatic system, such as the episcleral lymphatic network. Moreover,deployment of an intraocular shunt such that the outlet terminates inthe intra-Tenon's space avoids having to pierce Tenon's capsule whichcan otherwise cause complications during glaucoma filtration surgery dueto its tough and fibrous nature.

Methods for Intra-Tenon's Shunt Placement

Some methods involve inserting into the eye a hollow shaft configured tohold an intraocular shunt. In certain embodiments, the hollow shaft is acomponent of a deployment device that may deploy the intraocular shunt.The shunt is then deployed from the shaft into the eye such that theshunt forms a passage from the anterior chamber to the intra-Tenon'sspace. The hollow shaft is then withdrawn from the eye.

Referring to FIGS. 8 and 9, which show an intraocular shunt placed intothe eye such that the shunt forms a passage for fluid drainage from theanterior chamber to the intra-Tenon's space. To place the shunt withinthe eye, a surgical intervention to implant the shunt is preformed thatinvolves inserting into the eye 102 a deployment device 100 that holdsan intraocular shunt 101, and deploying at least a portion of the shunt101 within intra-Tenon's space 108, within subconjunctival space 109beneath the conjunctiva 110. In certain embodiments, a hollow shaft 106of a deployment device 100 holding the shunt 101 enters the eye 102through the cornea 103 (ab interno approach). The shaft 106 is advancedacross the anterior chamber 104 (as depicted by the broken line) in whatis referred to as a transpupil implant insertion. The shaft 106 isadvanced through the sclera 105 until a distal portion of the shaft 106is in proximity to Tenon's capsule 107. After piercing the sclera 105with the hollow shaft 106 of the deployment device 100, resistance toadvancement of the shaft 106 encountered by an operator of thedeployment device 100 informs the operator that the shaft 106 hascontacted Tenon's capsule 107 and is thus in proximity to Tenon'scapsule 107.

Numerous techniques may be employed to ensure that after piercing thesclera 105, the hollow shaft 106 does not pierce Tenon's capsule 107. Incertain embodiments, some methods involve the use of a hollow shaft 106,in which a portion of the hollow shaft extends linearly along alongitudinal axis and at least one other portion of the shaft extendsoff the longitudinal axis. For example, the hollow shaft 106 may have abend in the distal portion of the shaft, a U-shape, or an arcuate orV-shape in at least a portion of the shaft. Examples of such hollowshafts 106 suitable for use with some methods include but are notlimited to the hollow shafts 106 depicted in FIGS. 6A-6C. In embodimentsin which the hollow shaft 106 has a bend at a distal portion of theshaft, intra-Tenon's shunt placement can be achieved by using the bentdistal portion of the shaft 106 to push Tenon's capsule 107 away fromthe sclera 105 without penetrating Tenon's capsule 107. In theseembodiments, the tip of the distal end of the shaft 106 does not contactTenon's capsule 107.

In other embodiments, a straight hollow shaft 106 having a beveled tipis employed. The angle of the beveled tip of the hollow shaft isconfigured such that after piercing the sclera 105, the hollow shaft 106does not pierce Tenon's capsule 107. In these embodiments, the shaft 106is inserted into the eye 102 and through the sclera 105 at an angle suchthat the bevel of the tip is parallel to Tenon's capsule 107, therebypushing Tenon's capsule 107 away from the sclera 105, rather thanpenetrating Tenon's capsule 107, and allowing for deployment of a distalportion of the shunt 101 into the intra-Tenon's space 108.

Once a distal portion of the hollow shaft 106 is within theintra-Tenon's space 108, at least a portion of the device is rotated,thereby reducing the friction between the portion of the device that isin contact with the scleral tissue and the scleral tissue itself.Reduction in friction allows for deployment of the shunt from the deviceand then removal of the device from the eye without disturbing thetissue of the eye. After rotating the device, the shunt 101 is thendeployed from the shaft 106 of the deployment device 100, producing aconduit between the anterior chamber 104 and the intra-Tenon's space 108to allow aqueous humor to drain from the anterior chamber 104 (See FIGS.8 and 9).

In another embodiment, some methods further involves injecting anaqueous solution into the eye below Tenon's capsule in order to balloonthe capsule away from the sclera. The increase in intra-Tenon's spacecaused by the ballooning of Tenon's capsule is helpful for positioningof the outlet of the shunt in the intra-Tenon's space. The solution isinjected prior to the shaft piercing the sclera and entering theintra-Tenon's space. Suitable aqueous solutions include but are notlimited to Dulbecco's Phosphate Buffered Saline (DPBS), Hank's BalancedSalt Solution (HBSS), Phosphate-Buffered Saline (PBS), Earle's BalancedSalt Solution (EBSS), or other balanced salt solutions known in the art.In some embodiments, some methods involve injecting a viscoelastic fluidinto the eye. Preferably, some methods are conducted without the use ofa viscoelastic fluid. Some methods can be conducted using any shuntdeployment device known in the art. Examples of deployment devices thatare suitable for use with some methods include but are not limited tothe devices described in U.S. Pat. No. 6,007,511, U.S. Pat. No.6,544,249, and U.S. Pat. Pub. No. US2008/0108933, the contents of eachof which are hereby incorporated by reference in their entireties.

In certain embodiments, to ensure proper positioning and functioning ofthe intraocular shunt, the depth of penetration through the sclera isimportant when conducting some methods. In one embodiment, the distaltip of the hollow shaft pierces the sclera without coring, removing orcausing major tissue distortion of the surrounding eye tissue. The shuntis then deployed from the shaft. Preferably, a distal portion of thehollow shaft (as opposed to the distal tip) completely penetrates thesclera before the shunt is deployed from the hollow shaft. In certainembodiments, the hollow shaft is a flat bevel needle, such as a needlehaving a triple-ground point. The tip bevel first pierces through thesclera making a horizontal slit. In a preferred embodiment of somemethods, the needle is advanced even further such that the entire flatbevel penetrates through the sclera, as shown in FIG. 10D, to spread andopen the tissue to a full circular diameter. The tip bevel portion 190and flat bevel portion 192 of a triple ground needle point, and theconfiguration of the shunt 194 disposed in the needle point, areexemplified as the gray shaded areas in FIGS. 10A-10C. Without intendingto be bound by any theory, if the scleral channel is not completelyforced open by the flat bevel portion of the needle, the material aroundthe opening may not be sufficiently stretched and a pinching of theimplant in that zone will likely occur, causing the shunt to fail. Fullpenetration of the flat bevel through the sclera causes minor distortionand trauma to the local area. However, this area ultimately surroundsand conforms to the shunt once the shunt is deployed in the eye.

FIG. 11A depicts an example of an intraocular shunt implanted in an eyein accordance with some methods using a triple ground need point with100% penetration of the flat bevel in the scleral channel. FIG. 11Bdepicts an example of a shunt implanted in an eye in accordance withsome methods using a triple ground needle point with approximately 50%penetration of the flat bevel in the scleral channel. As shown in FIG.11B, the shunt is almost completely pinched off as compared to the openshunt depicted in FIG. 11A.

Some methods may be conducted using any commercially available shunts,such as the Optonol Ex-PRESS mini Glaucoma shunt, and the Solx DeepLightGold Micro-Shunt. However, some methods are preferably conducted usingthe intraocular shunts of some embodiments, as described herein.

Intraocular Shunts

The present inventions also provide intraocular shunts that areconfigured to form a drainage pathway from the anterior chamber of theeye to the intra-Tenon's space. In particular, the intraocular someembodiments of the shunt have a length that is sufficient to form adrainage pathway from the anterior chamber of the eye to theintra-Tenon's space. The length of the shunt is important in achievingplacement specifically in the intra-Tenon's space. A shunt that is toolong will extend beyond the intra-Tenon's space and irritate theconjunctiva, which can cause the filtration procedure to fail, aspreviously described. A shunt that is too short will not providesufficient access to drainage pathways such as the episcleral lymphaticsystem or the conjunctival lymphatic system.

Some embodiments of the shunt may be any length that allows for drainageof aqueous humor from an anterior chamber of an eye to the intra-tenon'sspace. Exemplary shunts range in length from approximately 0.5 mm toapproximately 20 mm or between approximately 4 mm to approximately 16mm, or any specific value within said ranges. In certain embodiments,the length of the shunt is between approximately 6 to 8 mm, or anyspecific value within said range, e.g., 6.0 mm, 6.1 mm, 6.2 mm, 6.3 mm,6.4 mm, 6.5 mm, 6.6 mm, 6.7 mm, 6.8 mm, 6.9 mm, 7 mm, 7.1 mm, 7.2 mm,7.3 mm, 7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8 mm. 7.9 mm, or 8.0 mm.

The intraocular some embodiments of the shunt are particularly suitablefor use in an ab interno glaucoma filtration procedure. Commerciallyavailable shunts that are currently used in ab interno filtrationprocedures are typically made of a hard, inflexible material such asgold, polymer, titanium, or stainless steel, and cause substantialirritation of the eye tissue, resulting in ocular inflammation such assubconjunctival blebbing or endophthalmitis. In contrast, theintraocular some embodiments of the shunt are flexible, and have anelasticity modulus that is substantially identical to the elasticitymodulus of the surrounding tissue in the implant site. As such, theintraocular some embodiments of the shunt are easily bendable, do noterode or cause a tissue reaction, and do not migrate once implanted.Thus, when implanted in the eye using an ab interno procedure, such asthe methods described herein, the intraocular some embodiments of theshunt do not induce substantial ocular inflammation such assubconjunctival blebbing or endophthalmitis. Additional exemplaryfeatures of the intraocular some embodiments of the shunt are discussedin further detail below.

Tissue Compatible Shunts

In certain aspects, some embodiments generally provide shunts composedof a material that has an elasticity modulus that is compatible with anelasticity modulus of tissue surrounding the shunt (e.g., tissuesurrounding the suprachoroidal space). In this manner, some embodimentsof the shunt are flexibility matched with the surrounding tissue, andthus will remain in place after implantation without the need for anytype of anchor that interacts with the surrounding tissue. Consequently,some embodiments of the shunt will maintain fluid flow away for ananterior chamber of the eye after implantation without causingirritation or inflammation to the tissue surrounding the eye.

Elastic modulus, or modulus of elasticity, is a mathematical descriptionof an object or substance's tendency to be deformed elastically when aforce is applied to it. The elastic modulus of an object is defined asthe slope of its stress-strain curve in the elastic deformation region:

$\lambda \overset{def}{=}\frac{Stress}{Strain}$

where lambda (λ) is the elastic modulus; stress is the force causing thedeformation divided by the area to which the force is applied; andstrain is the ratio of the change caused by the stress to the originalstate of the object. The elasticity modulus may also be known as Young'smodulus (E), which describes tensile elasticity, or the tendency of anobject to deform along an axis when opposing forces are applied alongthat axis. Young's modulus is defined as the ratio of tensile stress totensile strain. For further description regarding elasticity modulus andYoung's modulus, see for example Gere (Mechanics of Materials, 6thEdition, 2004, Thomson), the content of which is incorporated byreference herein in its entirety.

The elasticity modulus of any tissue can be determined by one of skillin the art. See for example Samani et al. (Phys. Med. Biol. 48:2183,2003); Erkamp et al. (Measuring The Elastic Modulus Of Small TissueSamples, Biomedical Engineering Department and Electrical Engineeringand Computer Science Department University of Michigan Ann Arbor, Mich.48109-2125; and Institute of Mathematical Problems in Biology RussianAcademy of Sciences, Pushchino, Moscow Region 142292 Russia); Chen etal. (IEEE Trans. Ultrason. Ferroelec. Freq. Control 43:191-194, 1996);Hall, (In 1996 Ultrasonics Symposium Proc., pp. 1193-1196, IEEE Cat. No.96CH35993, IEEE, New York, 1996); and Parker (Ultrasound Med. Biol.16:241-246, 1990), each of which provides methods of determining theelasticity modulus of body tissues. The content of each of these isincorporated by reference herein in its entirety.

The elasticity modulus of tissues of different organs is known in theart. For example, Pierscionek et al. (Br J Ophthalmol, 91:801-803, 2007)and Friberg (Experimental Eye Research, 473:429-436, 1988) show theelasticity modulus of the cornea and the sclera of the eye. The contentof each of these references is incorporated by reference herein in itsentirety. Chen, Hall, and Parker show the elasticity modulus ofdifferent muscles and the liver. Erkamp shows the elasticity modulus ofthe kidney.

Some embodiments of the shunt are composed of a material that iscompatible with an elasticity modulus of tissue surrounding the shunt.In certain embodiments, the material has an elasticity modulus that issubstantially identical to the elasticity modulus of the tissuesurrounding the shunt. In other embodiments, the material has anelasticity modulus that is greater than the elasticity modulus of thetissue surrounding the shunt. Exemplary materials includes biocompatiblepolymers, such as polycarbonate, polyethylene, polyethyleneterephthalate, polyimide, polystyrene, polypropylene,poly(styrene-b-isobutylene-b-styrene), or silicone rubber.

In particular embodiments, some embodiments of the shunt are composed ofa material that has an elasticity modulus that is compatible with theelasticity modulus of tissue in the eye, particularly scleral tissue. Incertain embodiments, compatible materials are those materials that aresofter than scleral tissue or marginally harder than scleral tissue, yetsoft enough to prohibit shunt migration. The elasticity modulus foranterior scleral tissue is approximately 2.9±1.4×106 N/m2, and1.8±1.1×106 N/m2 for posterior scleral tissue. See Friberg (ExperimentalEye Research, 473:429-436, 1988). An exemplary material is cross linkedgelatin derived from Bovine or Porcine Collagen.

Some embodiments encompasses shunts of different shapes and differentdimensions, and some embodiments of the shunt may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from diameter from approximately 100 μm to approximately 450such as approximately 190 μm to approximately 300 μm, and a length fromapproximately 0.5 mm to approximately 20 mm, such as from approximately2 mm to approximately 10 mm.

Shunts Reactive to Pressure

In other aspects, some embodiments generally provide shunts in which aportion of the shunt is composed of a flexible material that is reactiveto pressure, i.e., the diameter of the flexible portion of the shuntfluctuates depending upon the pressures exerted on that portion of theshunt. FIG. 12 provides a schematic of a shunt 223 having a flexibleportion 251. In this figure, the flexible portion 251 is shown in themiddle of the shunt 223. However, the flexible portion 251 may belocated in any portion of the shunt, such as the proximal or distalportion of the shunt. In certain embodiments, the entire shunt iscomposed of the flexible material, and thus the entire shunt is flexibleand reactive to pressure.

The flexible portion 251 of the shunt 223 acts as a valve that regulatesfluid flow through the shunt. The human eye produces aqueous humor at arate of about 2 μl/min for approximately 3 ml/day. The entire aqueousvolume is about 0.25 ml. When the pressure in the anterior chamber fallsafter surgery to about 7-8 mmHg, it is assumed the majority of theaqueous humor is exiting the eye through the implant since venousbackpressure prevents any significant outflow through normal drainagestructures (e.g., the trabecular meshwork).

After implantation, intraocular shunts have pressure exerted upon themby tissues surrounding the shunt (e.g., scleral tissue such as thesclera channel and the sclera exit) and pressure exerted upon them byaqueous humor flowing through the shunt. The flow through the shunt, andthus the pressure exerted by the fluid on the shunt, is calculated bythe equation:

$\Phi = {\frac{V}{T} = {{v\; \pi \; R^{2}} = {{\frac{\pi \; R^{4}}{8\eta}( \frac{{- \Delta}\; P}{\Delta \; x} )} = {\frac{\pi \; R^{4}}{8\eta}\frac{| {\Delta \; P} |}{L}}}}}$

where Φ is the volumetric flow rate; V is a volume of the liquid poured(cubic meters); t is the time (seconds); v is mean fluid velocity alongthe length of the tube (meters/second); x is a distance in direction offlow (meters); R is the internal radius of the tube (meters); ΔP is thepressure difference between the two ends (pascals); 11 is the dynamicfluid viscosity (pascal-second (Pa·s)); and L is the total length of thetube in the x direction (meters).

FIG. 13A provides a schematic of a shunt 226 implanted into an eye forregulation of fluid flow from the anterior chamber of the eye to an areaof lower pressure (e.g., the intra-Tenon's space, the subconjunctivalspace, the episcleral vein, the suprachoroidal space, or Schlemm'scanal). In certain embodiments, the area of lower pressure is thesubarachnoid space. The shunt is implanted such that a proximal end 227of the shunt 226 resides in the anterior chamber 228 of the eye, and adistal end 229 of the shunt 226 resides outside of the anterior chamberto conduct aqueous humor from the anterior chamber to an area of lowerpressure. A flexible portion 230 of the shunt 226 spans at least aportion of the sclera of the eye. As shown in FIG. 13A, the flexibleportion spans an entire length of the sclera 221.

When the pressure exerted on the flexible portion 230 of the shunt 226by sclera 231 (vertical arrows) is greater than the pressure exerted onthe flexible portion 230 of the shunt 226 by the fluid flowing throughthe shunt (horizontal arrow), the flexible portion 230 decreases indiameter, restricting flow through the shunt 226 (FIG. 13B). Therestricted flow results in aqueous humor leaving the anterior chamber228 at a reduced rate.

When the pressure exerted on the flexible portion 230 of the shunt 226by the fluid flowing through the shunt (horizontal arrow) is greaterthan the pressure exerted on the flexible portion 230 of the shunt 226by the sclera 231 (vertical arrows), the flexible portion 230 increasesin diameter, increasing flow through the shunt 226 (FIG. 13C). Theincreased flow results in aqueous humor leaving the anterior chamber 228at an increased rate.

Some embodiments encompasses shunts of different shapes and differentdimensions, and some embodiments of the shunt may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from diameter from approximately 100 μm to approximately 450μm, such as approximately 190 μm to approximately 300 μm, and a lengthfrom approximately 0.5 mm to approximately 20 mm, such as fromapproximately 2 mm to approximately 10 mm.

In a particular embodiments, the shunt has a length of about 6 mm and aninner diameter of about 64 μm. With these dimensions, the pressuredifference between the proximal end of the shunt that resides in theanterior chamber and the distal end of the shunt that resides outsidethe anterior chamber is about 4.3 mmHg. Such dimensions thus allow theimplant to act as a controlled valve and protect the integrity of theanterior chamber.

It will be appreciated that different dimensioned implants may be used.For example, shunts that range in length from about 0.5 mm to about 20mm, such as from about 2 mm to about 10 mm, and have a range in innerdiameter from about 10 μm to about 100 μm allow for pressure controlfrom approximately 0.5 mmHg to approximately 20 mmHg.

The material of the flexible portion and the thickness of the wall ofthe flexible portion will determine how reactive the flexible portion isto the pressures exerted upon it by the surrounding tissue and the fluidflowing through the shunt. Generally, with a certain material, thethicker the flexible portion, the less responsive the portion will be topressure. In certain embodiments, the flexible portion is a gelatin orother similar material, and the thickness of the gelatin materialforming the wall of the flexible portion ranges from about 10 μm thickto about 100 μm thick.

In a certain embodiment, the gelatin used for making the flexibleportion is known as gelatin Type B from bovine skin. An exemplarygelatin is PB Leiner gelatin from bovine skin, Type B, 225 Bloom, USP.Another material that may be used in the making of the flexible portionis a gelatin Type A from porcine skin, also available from SigmaChemical. Such gelatin is available from Sigma Chemical Company of St.Louis, Mo. under Code G-9382. Still other suitable gelatins includebovine bone gelatin, porcine bone gelatin and human-derived gelatins. Inaddition to gelatins, the flexible portion may be made of hydroxypropylmethylcellulose (HPMC), collagen, polylactic acid, polylglycolic acid,hyaluronic acid and glycosaminoglycans.

In certain embodiments, the gelatin is cross-linked. Cross-linkingincreases the inter- and intramolecular binding of the gelatinsubstrate. Any method for cross-linking the gelatin may be used. In aparticular embodiment, the formed gelatin is treated with a solution ofa cross-linking agent such as, but not limited to, glutaraldehyde. Othersuitable compounds for cross-linking include1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). Cross-linking byradiation, such as gamma or electron beam (e-beam) may be alternativelyemployed.

In one embodiment, the gelatin is contacted with a solution ofapproximately 25% glutaraldehyde for a selected period of time. Onesuitable form of glutaraldehyde is a grade 1G5882 glutaraldehydeavailable from Sigma Aldridge Company of Germany, although otherglutaraldehyde solutions may also be used. The pH of the glutaraldehydesolution should be in the range of 7 to 7.8 and, more particularly,7.35-7.44 and typically approximately 7.4+/−0.01. If necessary, the pHmay be adjusted by adding a suitable amount of a base such as sodiumhydroxide as needed.

Methods for forming the flexible portion of the shunt are shown forexample in Yu et al. (U.S. Pat. Pub. No. 2008/0108933), the content ofwhich is incorporated by reference herein in its entirety. In anexemplary protocol, the flexible portion may be made by dipping a coreor substrate such as a wire of a suitable diameter in a solution ofgelatin. The gelatin solution is typically prepared by dissolving agelatin powder in de-ionized water or sterile water for injection andplacing the dissolved gelatin in a water bath at a temperature ofapproximately 55° C. with thorough mixing to ensure complete dissolutionof the gelatin. In one embodiment, the ratio of solid gelatin to wateris approximately 10% to 50% gelatin by weight to 50% to 90% by weight ofwater. In an embodiment, the gelatin solution includes approximately 40%by weight, gelatin dissolved in water. The resulting gelatin solutionshould be devoid of air bubbles and has a viscosity that is betweenapproximately 200-500 cp and more particularly between approximately 260and 410 cp (centipoise).

Once the gelatin solution has been prepared, in accordance with themethod described above, supporting structures such as wires having aselected diameter are dipped into the solution to form the flexibleportion. Stainless steel wires coated with a biocompatible, lubriciousmaterial such as polytetrafluoroethylene (Teflon) are preferred.

Typically, the wires are gently lowered into a container of the gelatinsolution and then slowly withdrawn. The rate of movement is selected tocontrol the thickness of the coat. In addition, it is preferred that thetube be removed at a constant rate in order to provide the desiredcoating. To ensure that the gelatin is spread evenly over the surface ofthe wire, in one embodiment, the wires may be rotated in a stream ofcool air which helps to set the gelatin solution and affix film onto thewire. Dipping and withdrawing the wire supports may be repeated severaltimes to further ensure even coating of the gelatin. Once the wires havebeen sufficiently coated with gelatin, the resulting gelatin films onthe wire may be dried at room temperature for at least 1 hour, and morepreferably, approximately 10 to 24 hours. Apparatus for forming gelatintubes are described in Yu et al. (U.S. Pat. Pub. No. 2008/0108933).

Once dried, the formed flexible portions may be treated with across-linking agent. In one embodiment, the formed flexible portion maybe cross-linked by dipping the wire (with film thereon) into the 25%glutaraldehyde solution, at pH of approximately 7.0-7.8 and morepreferably approximately 7.35-7.44 at room temperature for at least 4hours and preferably between approximately 10 to 36 hours, depending onthe degree of cross-linking desired. In one embodiment, the formedflexible portion is contacted with a cross-linking agent such asgluteraldehyde for at least approximately 16 hours. Cross-linking canalso be accelerated when it is performed a high temperatures. It isbelieved that the degree of cross-linking is proportional to thebioabsorption time of the shunt once implanted. In general, the morecross-linking, the longer the survival of the shunt in the body.

The residual glutaraldehyde or other cross-linking agent is removed fromthe formed flexible portion by soaking the tubes in a volume of sterilewater for injection. The water may optionally be replaced at regularintervals, circulated or re-circulated to accelerate diffusion of theunbound glutaraldehyde from the tube. The tubes are washed for a periodof a few hours to a period of a few months with the ideal time being3-14 days. The now cross-linked gelatin tubes may then be dried (cured)at ambient temperature for a selected period of time. It has beenobserved that a drying period of approximately 48-96 hours and moretypically 3 days (i.e., 72 hours) may be preferred for the formation ofthe cross-linked gelatin tubes.

Where a cross-linking agent is used, it may be desirable to include aquenching agent in the method of making the flexible portion. Quenchingagents remove unbound molecules of the cross-linking agent from theformed flexible portion. In certain cases, removing the cross-linkingagent may reduce the potential toxicity to a patient if too much of thecross-linking agent is released from the flexible portion. In certainembodiments, the formed flexible portion is contacted with the quenchingagent after the cross-linking treatment and, may be included with thewashing/rinsing solution. Examples of quenching agents include glycineor sodium borohydride.

The formed flexible portion may be further coated or impregnated withbiologics and/or pharmaceuticals, as discussed herein.

After the requisite drying period, the formed and cross-linked flexibleportion is removed from the underlying supports or wires. In oneembodiment, wire tubes may be cut at two ends and the formed gelatinflexible portion slowly removed from the wire support. In anotherembodiment, wires with gelatin film thereon, may be pushed off using aplunger or tube to remove the formed gelatin flexible portion.

Multi-Port Shunts

Other aspects of some embodiments generally provide multi-port shunts.Such shunts reduce probability of the shunt clogging after implantationbecause fluid can enter or exit the shunt even if one or more ports ofthe shunt become clogged with particulate. In certain embodiments, theshunt includes a hollow body defining a flow path and more than twoports, in which the body is configured such that a proximal portionreceives fluid from the anterior chamber of an eye and a distal portiondirects the fluid to a location of lower pressure with respect to theanterior chamber. Exemplary areas of lower pressure includeintra-Tenon's space, the subconjunctival space, the episcleral vein, thesuprachoroidal space, Schlemm's canal, or drainage structures associatedwith the intra-scleral space. Another exemplary area of lower pressureto which fluid may be drained is the subarachnoid space.

The shunt may have many different configurations. FIG. 14A shows anembodiment of a shunt 232 in which the proximal portion of the shunt(i.e., the portion disposed within the anterior chamber of the eye)includes more than one port (designated as numbers 233 a to 233 e) andthe distal portion of the shunt (i.e., the portion that is located inthe intra-Tenon's space) includes a single port 234. FIG. 14B showsanother embodiment of a shunt 232 in which the proximal portion includesa single port 233 and the distal portion includes more than one port(designated as numbers 234 a to 234 e). FIG. 14C shows anotherembodiment of a shunt 232 in which the proximal portions include morethan one port (designated as numbers 233 a to 233 e) and the distalportions include more than one port (designated as numbers 234 a to 234e). While FIGS. 14A-14C show shunts that have five ports at the proximalportion, distal portion, or both, those shunts are only exemplaryembodiments. The ports may be located along any portion of the shunt,and some embodiments of the shunt include all shunts having more thantwo ports. For example, some embodiments of the shunt may include atleast three ports, at least four ports, at least five ports, at least 10ports, at least 15 ports, or at least 20 ports.

The ports may be positioned in various different orientations and alongvarious different portions of the shunt. In certain embodiments, atleast one of the ports is oriented at an angle to the length of thebody. In certain embodiments, at least one of the ports is oriented 90°to the length of the body. See for example FIG. 14A, which depicts ports233 a, 233 b, 233 d, and 233 e as being oriented at a 90° angle to port233 c.

The ports may have the same or different inner diameters. In certainembodiments, at least one of the ports has an inner diameter that isdifferent from the inner diameters of the other ports. FIGS. 15A-15Bshow embodiments of a shunt 232 having multiple ports (233 a and 233 b)at a proximal end and a single port 234 at a distal end. FIG. 15A showsthat port 233 b has an inner diameter that is different from the innerdiameters of ports 233 a and 234. In this figure, the inner diameter ofport 233 b is less than the inner diameter of ports 233 a and 234. Anexemplary inner diameter of port 233 b is from about 20 μm to about 40particularly about 30 In other embodiments, the inner diameter of port33 b is greater than the inner diameter of ports 233 a and 234. See forexample FIG. 15B.

Some embodiments encompasses shunts of different shapes and differentdimensions, and some embodiments of the shunt may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 an outsidediameter from approximately 190 μm to approximately 300 and a lengthfrom approximately 0.5 mm to approximately 20 mm. Some embodiments ofthe shunt may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Shunts with Overflow Ports

Other aspects of some embodiments generally provide shunts with overflowports. Those shunts are configured such that the overflow port remainspartially or completely closed until there is a pressure build-up withinthe shunt sufficient to force open the overflow port. Such pressurebuild-up typically results from particulate partially or fully cloggingan entry or an exit port of the shunt. Such shunts reduce probability ofthe shunt clogging after implantation because fluid can enter or exitthe shunt by the overflow port even if one port of the shunt becomesclogged with particulate.

In certain embodiments, the shunt includes a hollow body defining aninlet configured to receive fluid from an anterior chamber of an eye andan outlet configured to direct the fluid to the intra-Tenon's orintrascleral space, or other areas of lower pressure disclosed herein,the body further including at least one slit. The slit may be located atany place along the body of the shunt. FIG. 16A shows a shunt 235 havingan inlet 236, an outlet 237, and a slit 238 located in proximity to theinlet 236. FIG. 16B shows a shunt 235 having an inlet 236, an outlet237, and a slit 239 located in proximity to the outlet 237. FIG. 16Cshows a shunt 235 having an inlet 236, an outlet 237, a slit 238 locatedin proximity to the inlet 236, and a slit 239 located in proximity tothe outlet 237.

While FIGS. 16A-16B show shunts have only a single overflow port at theproximal portion, the distal portion, or both the proximal and distalportions, those shunts are only exemplary embodiments. The overflowport(s) may be located along any portion of the shunt, and someembodiments of the shunt include shunts having more than one overflowport. In certain embodiments, some embodiments of the shunt include morethan one overflow port at the proximal portion, the distal portion, orboth. For example, FIG. 17 shows a shunt 240 having an inlet 241, anoutlet 242, and slits 243 a and 243 b located in proximity to the inlet241. Some embodiments of the shunt may include at least two overflowports, at least three overflow ports, at least four overflow ports, atleast five overflow ports, at least 10 overflow ports, at least 15overflow ports, or at least 20 overflow ports. In certain embodiments,some embodiments of the shunt include two slits that overlap and areoriented at 90° to each other, thereby forming a cross.

In certain embodiments, the slit may be at the proximal or the distalend of the shunt, producing a split in the proximal or the distal end ofthe implant. FIG. 18 shows an embodiment of a shunt 244 having an inlet245, outlet 246, and a slit 247 that is located at the proximal end ofthe shunt, producing a split in the inlet 245 of the shunt.

In certain embodiments, the slit has a width that is substantially thesame or less than an inner diameter of the inlet. In other embodiments,the slit has a width that is substantially the same or less than aninner diameter of the outlet. In certain embodiments, the slit has alength that ranges from about 0.05 mm to about 2 mm, and a width thatranges from about 10 μm to about 200 μm. Generally, the slit does notdirect the fluid unless the outlet is obstructed. However, the shunt maybe configured such that the slit does direct at least some of the fluideven if the inlet or outlet is not obstructed.

Some embodiments encompasses shunts of different shapes and differentdimensions, and some embodiments of the shunt may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from diameter from approximately 100 μm to approximately 450μm, such as approximately 190 μm to approximately 300 μm, and a lengthfrom approximately 0.5 mm to approximately 20 mm, such as fromapproximately 2 mm to approximately 10 mm. Some embodiments of the shuntmay be made from any biocompatible material. An exemplary material isgelatin. Methods of making shunts composed of gelatin are describedabove.

Shunts Having a Variable Inner Diameter

In other aspects, some embodiments generally provide a shunt having avariable inner diameter. In particular embodiments, the diameterincreases from inlet to outlet of the shunt. By having a variable innerdiameter that increases from inlet to outlet, a pressure gradient isproduced and particulate that may otherwise clog the inlet of the shuntis forced through the inlet due to the pressure gradient. Further, theparticulate will flow out of the shunt because the diameter onlyincreases after the inlet.

FIGS. 19A-19B show embodiments of a shunt 248 having an inlet 249configured to receive fluid from an anterior chamber of an eye and anoutlet 250 configured to direct the fluid to a location of lowerpressure with respect to the anterior chamber, in which the body furtherincludes a variable inner diameter that increases along the length ofthe body from the inlet 249 to the outlet 250. In certain embodiments,the inner diameter continuously increases along the length of the body,for example as shown in FIG. 19A. In other embodiments, the innerdiameter remains constant along portions of the length of the body, asshown in FIG. 19B.

In exemplary embodiments, the inner diameter may range in size fromabout 10 μm to about 200 μm, and the inner diameter at the outlet mayrange in size from about 15 μm to about 300 μm. Some embodimentsencompasses shunts of different shapes and different dimensions, andsome embodiments of the shunt may be any shape or any dimension that maybe accommodated by the eye. In certain embodiments, the intraocularshunt is of a cylindrical shape and has an outside cylindrical wall anda hollow interior. The shunt may have an inside diameter fromapproximately 10 μm to approximately 250 μm, an outside diameter fromdiameter from approximately 100 μm to approximately 450 μm, such asapproximately 190 μm to approximately 300 μm, and a length fromapproximately 0.5 mm to approximately 20 mm, such as from approximately2 mm to approximately 10 mm. Some embodiments of the shunt may be madefrom any biocompatible material. An exemplary material is gelatin.Methods of making shunts composed of gelatin are described above.

Shunts Having Pronged Ends

In other aspects, some embodiments generally provide shunts forfacilitating conduction of fluid flow away from an organ, the shuntincluding a body, in which at least one end of the shunt is shaped tohave a plurality of prongs. Such shunts reduce probability of the shuntclogging after implantation because fluid can enter or exit the shunt byany space between the prongs even if one portion of the shunt becomesclogged with particulate.

FIGS. 20A-20D show embodiments of a shunt 252 in which at least one endof the shunt 252 includes a plurality of prongs 253 a-d. FIGS. 20A-20Dshow embodiments in which both a proximal end and a distal end of theshunt are shaped to have the plurality of prongs. However, numerousdifferent configurations are envisioned. For example, in certainembodiments, only the proximal end of the shunt is shaped to have theplurality of prongs. In other embodiments, only the distal end of theshunt is shaped to have the plurality of prongs.

Prongs 253 a-d can have any shape (i.e., width, length, height). FIGS.20A-20B show prongs 253 a-d as straight prongs. In this embodiment, thespacing between the prongs 253 a-d is the same. In another embodimentshown in FIGS. 20C-20D, prongs 253 a-d are tapered. In this embodiment,the spacing between the prongs increases toward a proximal and/or distalend of the shunt 252.

FIGS. 20A-20D show embodiments that include four prongs. However, someembodiments of the shunt may accommodate any number of prongs, such astwo prongs, three prongs, four prongs, five prongs, six prongs, sevenprongs, eight prongs, nine prongs, ten prongs, etc. The number of prongschosen will depend on the desired flow characteristics of the shunt.

Some embodiments encompass shunts of different shapes and differentdimensions, and some embodiments of the shunt may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 100 μm to approximately 450 μm, and a lengthfrom approximately 2 mm to approximately 10 mm. Some embodiments of theshunt may be made from any biocompatible material. An exemplary materialis gelatin. Methods of making shunts composed of gelatin are describedabove.

Shunts Having a Longitudinal Slit

In other aspects, some embodiments generally provide a shunt fordraining fluid from an anterior chamber of an eye that includes a hollowbody defining an inlet configured to receive fluid from an anteriorchamber of the eye and an outlet configured to direct the fluid to alocation of lower pressure with respect to the anterior chamber; theshunt being configured such that at least one end of the shunt includesa longitudinal slit. Such shunts reduce probability of the shuntclogging after implantation because the end(s) of the shunt can moreeasily pass particulate which would generally clog a shunt lacking theslits.

FIGS. 21A-21D show embodiments of a shunt 254 in which at least one endof the shunt 254 includes a longitudinal slit 255 that produces a topportion 256 a and a bottom portion 256 b in a proximal and/or distal endof the shunt 254. FIGS. 21A-21D show an embodiment in which both aproximal end and a distal end include a longitudinal slit 255 thatproduces a top portion 256 a and a bottom portion 256 b in both ends ofthe shunt 254. However, numerous different configurations areenvisioned. For example, in certain embodiments, only the proximal endof the shunt includes longitudinal slit 255. In other embodiments, onlythe distal end of the shunt includes longitudinal slit 255.

Longitudinal slit 255 can have any shape (i.e., width, length, height).FIGS. 21A-21B show a longitudinal slit 255 that is straight such thatthe space between the top portion 256 a and the bottom portion 256 bremains the same along the length of the slit 255. In another embodimentshown in FIGS. 21C-21D, longitudinal slit 255 is tapered. In thisembodiment, the space between the top portion 245 a and the bottomportion 256 b increases toward a proximal and/or distal end of the shunt254.

Some embodiments encompass shunts of different shapes and differentdimensions, and some embodiments of the shunt may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 100 μm to approximately 450 μm, and a lengthfrom approximately 2 mm to approximately 10 mm. Some embodiments of theshunt may be made from any biocompatible material. An exemplary materialis gelatin. Methods of making shunts composed of gelatin are describedabove.

Pharmaceutical Agents

In certain embodiments, some embodiments of the shunt may be coated orimpregnated with at least one pharmaceutical and/or biological agent ora combination thereof. The pharmaceutical and/or biological agent maycoat or impregnate an entire exterior of the shunt, an entire interiorof the shunt, or both. Alternatively, the pharmaceutical or biologicalagent may coat and/or impregnate a portion of an exterior of the shunt,a portion of an interior of the shunt, or both. Methods of coatingand/or impregnating an intraocular shunt with a pharmaceutical and/orbiological agent are known in the art. See for example, Darouiche (U.S.Pat. Nos. 7,790,183; 6,719,991; 6,558,686; 6,162,487; 5,902,283;5,853,745; and 5,624,704) and Yu et al. (U.S. Pat. Pub. No.2008/0108933). The content of each of these references is incorporatedby reference herein its entirety.

In certain embodiments, the exterior portion of the shunt that residesin the anterior chamber after implantation (e.g., about 1 mm of theproximal end of the shunt) is coated and/or impregnated with thepharmaceutical or biological agent. In other embodiments, the exteriorof the shunt that resides in the scleral tissue after implantation ofthe shunt is coated and/or impregnated with the pharmaceutical orbiological agent. In other embodiments, the exterior portion of theshunt that resides in the area of lower pressure, such as theintrascleral space, the intra-Tenon's space, or the subconjunctivalspace, after implantation is coated and/or impregnated with thepharmaceutical or biological agent. In embodiments in which thepharmaceutical or biological agent coats and/or impregnates the interiorof the shunt, the agent may be flushed through the shunt and into thearea of lower pressure (e.g., the intra-Tenon's space or thesubconjunctival space).

Any pharmaceutical and/or biological agent or combination thereof may beused with some embodiments of the shunt. The pharmaceutical and/orbiological agent may be released over a short period of time (e.g.,seconds) or may be released over longer periods of time (e.g., days,weeks, months, or even years). Exemplary agents include anti-mitoticpharmaceuticals such as Mitomycin-C or 5-Fluorouracil, anti-VEGF (suchas Lucintes, Macugen, Avastin, VEGF or steroids).

Reference is now made to FIG. 22A which shows an embodiment of a shuntdeployment device 300 according to some embodiments. In someembodiments, the device 300 may be used to re-open a partially orcompletely closed anterior chamber angle and deploy an intraocularshunt. While FIG. 22A shows a handheld manually operated shuntdeployment device, it will be appreciated that some embodiments of thedevice may be coupled with robotic systems and may be completely orpartially automated. As shown in FIG. 22A deployment device 300 includesa generally cylindrical body or housing 301, however, the body shape ofhousing 301 could be other than cylindrical. Housing 301 may have anergonomical shape, allowing for comfortable grasping by an operator.Housing 301 is shown with optional grooves 302 to allow for easiergripping by a surgeon.

FIG. 22B shows a cross sectional view of device 300. This figure showsthat housing 301 includes a proximal portion 301 a and a distal portion301 b. The distal portion 301 b is movable within proximal portion 301a. In this figure, spring mechanism 320 includes a spring 321 thatcontrols movement of distal portion 301 b. Spring mechanism 320 furtherincludes a member 322 that acts as a stopper and limits axial retractionof distal portion 301 b within proximal portion 301 a. Spring mechanism320 further includes members 323 and 324 that run the length of spring321. The ends of members 323 and 324 include flanges 325 and 326 thatproject inward from members 323 and 324. An end of distal portion 301 bincludes flanges 327 and 328 that project outward from distal portion301 b. Flanges 325 and 326 interact with flanges 327 and 328 to preventrelease of distal portion 301 b from proximal portion 301 a. The flanges325 and 326 and 327 and 328 hold the distal portion 301 b in an extendedposition until a compressive force acts upon distal portion 301 b,thereby causing distal portion 301 b to partially retract withinproximal portion 301 a.

Distal portion 301 b includes a capsule 329 and a hollow sleeve 330.Capsule 329 and sleeve 330 may be formed integrally or may be separatecomponents that are coupled or connected to each other. The hollowsleeve 330 is configured for insertion into an eye and to extend into ananterior chamber of an eye. FIG. 22B shows distal portion 301 b ofhousing 301 extended from proximal portion 301 a of housing 301. In thisconfiguration, hollow shaft 304 (not shown in this figure) is completelydisposed within sleeve 330. FIG. 22C shows distal portion 301 b ofhousing 301 retracted within proximal portion 301 a of housing 301.Retraction of distal portion 301 b of housing 301 within proximalportion 301 a of housing 301 exposes hollow shaft 304, which isdiscussed in greater detail below.

The hollow shaft 304 may include a sharpened distal end. With referenceto FIG. 22D, the hollow shaft 304 may be flexible and pre-bent to followthe scleral spur down along the sclera upon extension of the hollowshaft 304 from the sleeve 330, which is discussed in greater detailbelow. The material used for the hollow shaft 304 may be any memoryshape material, such as spring steel, such that the hollow shaft 304 caneasily transform from its bent position to a straight cannula whenhoused within the sleeve 330.

A distal end of sleeve 330 may optionally include a protrusion 331 (FIG.22D). Protrusion 331 provides resistance feedback to an operator as theoperator is advancing the sleeve 330 through an anterior chamber of aneye. Further, protrusion 331 can be of a shape and size that it iscapable of re-opening a partially or completely closed anterior chamberangle of an eye as an operator is advancing the device 300 through ananterior chamber of an eye. In a standard ab interno approach (see, forexample, Yu et al. U.S. Pat. No. 6,544,249 and U.S. Pat. Pub. No.2008/0108933) a deployment device holding a shunt enters an eye througha cornea. The deployment device is advanced across the anterior chamberin what is referred to as a transpupil implant insertion. The deploymentdevice is advanced to the sclera on the opposite side of the eye fromwhich the device entered the eye. With some embodiments of the device,upon advancement of the device 300 across an anterior chamber of theeye, the protrusion 331 at the distal end of the hollow sleeve 330 willcontact the sclera, providing resistance feedback to an operator that nofurther advancement of the device 300 is necessary (see FIGS. 38A-38E).This feedback also informs the operator that the device 300 is in properposition for exposure of the hollow shaft 304, which will advancethrough the sclera for deployment of an intraocular shunt. Theprotrusion 331, provides adequate surface area at the distal end ofsleeve 330, thus preventing sleeve 330 from entering the sclera.

Further, in some embodiments, the deployment device can be advanced intothe anterior chamber angle on the opposite side of the eye from whichthe device entered the eye. With some embodiments of the device, uponadvancement of the device 300 across an anterior chamber of the eye, theprotrusion 331 at the distal end of the hollow sleeve 330 will contact apartially or completely closed anterior chamber angle, and continuedadvancement of the device 300 will result in the protrusion 331re-opening the partially or completely closed anterior chamber angle.Once re-opened by the protrusion 131, the device 300 can be moved intoproper position for exposure of the hollow shaft 304, which will advancethrough the sclera for deployment of an intraocular shunt. Theprotrusion 331, provides adequate surface area at the distal end ofsleeve 330, thus preventing sleeve 330 from entering the tissue of theeye that is blocking access the trabecular meshwork (e.g., the iris).

In certain embodiments, protrusion 331 has a substantially flat bottomportion and an angled top portion (FIG. 22E). In other embodiments,protrusion 331 has a slightly tapered top and a slightly tapered bottomwith a rounded distal portion (FIGS. 23A-23C).

Referring back to FIG. 22E, the angle of the top portion issubstantially identical to an anterior chamber angle of an eye. Such ashape of the protrusion ensures that some embodiments of the device willalso finds its way to fit, such as by conforming and sliding, into theanterior chamber angle of the eye, the place for proper deployment of anintraocular shunt. This is explained with reference to FIGS. 24A to 24E.FIG. 24A shows device 300 in an insertion configuration and insertedinto an eye 340. In this figure, protrusion 331 at the distal end of thesleeve 330 has been advanced across the anterior chamber 341 to thesclera 342 on the opposite side of the eye 340 from which the deviceentered the eye 340. FIG. 24A shows protrusion 331 fitted within theanterior chamber angle 343 of the eye 340. If sleeve 330 enters theanterior chamber 341 at too shallow an angle, i.e., the protrusion 331hit the sclera 342 above the anterior chamber angle 343, the angled topportion of the protrusion 331 causes the sleeve 330 to slide down thesclera 342 (direction of arrow) until the protrusion 331 is fit withinthe anterior chamber angle 343 of the eye 340 (FIGS. 24B and 24C). Thesleeve 330 will slide down the sclera 342 instead of entering the sclera342 at the contact point because the shaft 304 is completely disposedwithin the sleeve 330 and the protrusion 331 provides adequate surfacearea at the distal end of sleeve 330 to prevent enough force from beinggenerated at the distal end of sleeve 330 that would result in sleeve330 entering the sclera 342.

Conversely, if sleeve 330 enters the anterior chamber 341 at too steepan angle, i.e., the protrusion 331 hit the iris 344 below the anteriorchamber angle 343, the substantially flat bottom portion of theprotrusion 331 causes the sleeve 330 to deflect off the iris 344 andproceed is a direction parallel to the iris 344 until the protrusion 331is fit within the anterior chamber angle 343 of the eye 340 (FIGS. 24Dand 24E). The sleeve 330 will deflect off the iris 344 instead ofentering the iris 344 at the contact point because the shaft 304 iscompletely disposed within the sleeve 330 and the protrusion 331provides adequate surface area at the distal end of sleeve 330 toprevent enough force from being generated at the distal end of sleeve330 that would result in sleeve 330 entering the iris 344.

In certain embodiments, protrusion 331 is not required. In theseembodiments, the sleeve 330 is of a sufficient outer diameter such thatthe sleeve itself may serve the function of the protrusion as describedabove. In these embodiments, a distal end of the sleeve is shaped tohave a flat bottom portion and an angled top portion. In otherembodiments, a goniolens can be used to visualize advancement of thedevice within the eye, and thus the configuration of the distal end ofthe sleeve 330 is not important for proper shunt deployment using someembodiments of the device.

Referring back to FIG. 22A, the proximal portion 301 a of the housing301 is open at its proximal end, such that a portion of a deploymentmechanism 303 may extend from the proximal end of the proximal portion301 a of the housing 301. The sleeve 330 of the distal portion 301 b ofthe housing 301 is also open such that at least a portion of a hollowshaft 304 may extend inside the housing, into sleeve 330 of the distalportion 301 b of the housing 301, and extend beyond the distal end ofthe sleeve 330 in certain configurations (such as the deploymentconfiguration). Housing 301 further includes a slot 306 through which anoperator, such as a surgeon, using the device 300 may view an indicator307 on the deployment mechanism 303.

Housing 301 and protrusion 331 may be made of any material that issuitable for use in medical devices. For example, housing 301 andprotrusion 331 may be made of a lightweight aluminum or a biocompatibleplastic material. Examples of such suitable plastic materials includepolycarbonate and other polymeric resins such as DELRIN and ULTEM. Incertain embodiments, housing 301 and protrusion 331 are made of amaterial that may be autoclaved, and thus allow for housing 301 andprotrusion 331 to be re-usable. Alternatively, device 300, may be soldas a one-time-use device, and thus the material of the housing and theprotrusion does not need to be a material that is autoclavable.

Deployment into the eye of an intraocular shunt, such as the shuntsdescribed herein, in accordance with some methods can be achieved usinga hollow shaft configured to hold the shunt, as described herein. Thehollow shaft can be coupled to a deployment device or part of thedeployment device itself. Deployment devices that are suitable for usewith some methods include but are not limited to the deployment devicesdescribed in U.S. Pat. No. 6,007,511, U.S. Pat. No. 6,544,249, and U.S.Pat. Pub. No. US2008/0108933, the contents of each of which are herebyincorporated by reference in their entireties. In other embodiments, thedeployment devices are devices as described in co-pending and co-ownedU.S. patent application Ser. No. 12/946,222 filed on Nov. 15, 2010, theentire content of which is incorporated by reference herein.

In still other embodiments, some methods are conducted using thedeployment device 400 depicted in FIG. 25. While FIG. 25 shows ahandheld manually operated shunt deployment device, it will beappreciated that some embodiments of the device may be coupled withrobotic systems and may be completely or partially automated. As shownin FIG. 25, deployment device 400 includes a generally cylindrical bodyor housing 401, however, the body shape of housing 401 could be otherthan cylindrical. Housing 401 may have an ergonomical shape, allowingfor comfortable grasping by an operator. Housing 401 is shown withoptional grooves 402 to allow for easier gripping by a surgeon.

Housing 401 is shown having a larger proximal portion that tapers to adistal portion. The distal portion includes a hollow sleeve 405. Thehollow sleeve 405 is configured for insertion into an eye and to extendinto an anterior chamber of an eye. The hollow sleeve is visible withinan anterior chamber of an eye. The sleeve may include an edge at adistal end that provides resistance feedback to an operator uponinsertion of the deployment device 400 within an eye of a person. Uponadvancement of the device 400 across an anterior chamber of the eye, thehollow sleeve 405 will eventually contact the sclera, providingresistance feedback to an operator that no further advancement of thedevice 400 is necessary. The edge of the sleeve 405, prevents the shaft404 from accidentally being pushed too far through the sclera. Atemporary guard 408 is configured to fit around sleeve 405 and extendbeyond an end of sleeve 405. The guard is used during shipping of thedevice and protects an operator from a distal end of a hollow shaft 404that extends beyond the end of the sleeve 405. The guard is removedprior to use of the device.

Housing 401 is open at its proximal end, such that a portion of adeployment mechanism 403 may extend from the proximal end of the housing401. A distal end of housing 401 is also open such that at least aportion of a hollow shaft 404 may extend through and beyond the distalend of the housing 401. Housing 401 further includes a slot 406 throughwhich an operator, such as a surgeon, using the device 400 may view anindicator 407 on the deployment mechanism 403.

Housing 401 may be made of any material that is suitable for use inmedical devices. For example, housing 401 may be made of a lightweightaluminum or a biocompatible plastic material. Examples of such suitableplastic materials include polycarbonate and other polymeric resins suchas DELRIN and ULTEM. In certain embodiments, housing 401 is made of amaterial that may be autoclaved, and thus allow for housing 401 to bere-usable. Alternatively, device 400, may be sold as a one-time-usedevice, and thus the material of the housing does not need to be amaterial that is autoclavable.

Housing 401 may be made of multiple components that connect together toform the housing. FIG. 26 shows an exploded view of deployment device400. In this figure, housing 401, is shown having three components 401a, 401 b, and 401 c. The components are designed to screw together toform housing 401. FIG. 26 also shows deployment mechanism 403. Thehousing 401 is designed such that deployment mechanism 403 fits withinassembled housing 401. Housing 401 is designed such that components ofdeployment mechanism 403 are movable within housing 401.

FIGS. 27A-27D also show deployment mechanism 403. The housing 401 isdesigned such that deployment mechanism 403 fits within assembledhousing 401. Housing 401 is designed such that components of deploymentmechanism 403 are movable within housing 401.

FIGS. 27A-27D show different enlarged views of the deployment mechanism403. Deployment mechanism 403 may be made of any material that issuitable for use in medical devices. For example, deployment mechanism403 may be made of a lightweight aluminum or a biocompatible plasticmaterial. Examples of such suitable plastic materials includepolycarbonate and other polymeric resins such as DELRIN and ULTEM. Incertain embodiments, deployment mechanism 403 is made of a material thatmay be autoclaved, and thus allow for deployment mechanism 403 to bere-usable. Alternatively, device 400 may be sold as a one-time-usedevice, and thus the material of the deployment mechanism does not needto be a material that is autoclavable.

Deployment mechanism 403 includes a distal portion 409 and a distalportion 410. The deployment mechanism 403 is configured such that distalportion 409 is movable within distal portion 410. More particularly,distal portion 409 is capable of partially retracting to within distalportion 410.

In this embodiment, the distal portion 409 is shown to taper to aconnection with a hollow shaft 404. This embodiment is illustrated suchthat the connection between the hollow shaft 404 and the distal portion409 of the deployment mechanism 403 occurs inside the housing 401.Hollow shaft 404 may be removable from the distal portion 409 of thedeployment mechanism 403. Alternatively, the hollow shaft 404 may bepermanently coupled to the distal portion 409 of the deploymentmechanism 403.

Generally, hollow shaft 404 is configured to hold an intraocular shunt415. An exemplary intraocular shunt 415 in shown in FIG. 29. Otherexemplary intraocular shunts are shown in Yu et al. (U.S. Pat. Pub. No.2008/0108933). Generally, in one embodiment, intraocular shunts are of acylindrical shape and have an outside cylindrical wall and a hollowinterior. The shunt may have an inner diameter of approximately 50 μm toapproximately 250 μm, an outside diameter of approximately 190 μm toapproximately 300 μm, and a length of approximately 0.5 mm to about 20mm. Thus, hollow shaft 404 is configured to at least hold a shunt ofsuch shape and such dimensions. However, hollow shaft 404 may beconfigured to hold shunts of different shapes and different dimensionsthan those described above, and some embodiments encompass a shaft 404that may be configured to hold any shaped or dimensioned intraocularshunt. In particular embodiments, the shaft has an inner diameter ofapproximately 200 μm to approximately 400 μm. In certain embodiments,the shunt is a soft gel shunt, e.g., a gelatin shunt. If a gelatin shuntis used, the shunt is generally wetted inside the hollow shaft 404 witha balanced salt solution (e.g., Dulbecco's Phosphate Buffered Saline) ora steroid or other drug prior to implantation. Such priming ensures thatthe shunt remains flexible before implantation.

The shaft 404 may be any length. A usable length of the shaft may beanywhere from about 5 mm to about 40 mm, and is 15 mm in certainembodiments. In certain embodiments, the shaft is straight. In otherembodiments, shaft 404 is of a shape other than straight, for example ashaft having a bend along its length or a shaft having an arcuateportion. Exemplary shaped shafts are shown for example in Yu et al.(U.S. Pat. Pub. No. 2008/0108933). In particular embodiments, the shaftincludes a bend at a distal portion of the shaft. In other embodiments,a distal end of the shaft is beveled or is sharpened to a point.

The shaft 404 may hold the shunt at least partially within the hollowinterior of the shaft 404. In other embodiments, the shunt is heldcompletely within the hollow interior of the shaft 404. Alternatively,the hollow shaft may hold the shunt on an outer surface of the shaft404. In particular embodiments, the shunt is held within the hollowinterior of the shaft 404. In certain embodiments, the hollow shaft is aneedle having a hollow interior. Needles that are configured to hold anintraocular shunt are commercially available from Terumo Medical Corp.(Elkington, Md.).

A proximal portion of the deployment mechanism 403 includes optionalgrooves 416 to allow for easier gripping by an operator for easierrotation of the deployment mechanism, which will be discussed in moredetail below. The proximal portion 410 of the deployment mechanism alsoincludes at least one indicator that provides feedback to an operator asto the state of the deployment mechanism. The indicator may be any typeof indicator known in the art, for example a visual indicator, an audioindicator, or a tactile indicator. FIGS. 27A-27D show a deploymentmechanism having two indicators, a ready indicator 411 and a deployedindicator 419. Ready indicator 411 provides feedback to an operator thatthe deployment mechanism is in a configuration for deployment of anintraocular shunt from the deployment device 400. The ready indicator411 is shown in this embodiment as a green oval having a triangle withinthe oval. Deployed indicator 419 provides feedback to the operator thatthe deployment mechanism has been fully engaged and has deployed theshunt from the deployment device 400. The deployed indicator 419 isshown in this embodiment as a yellow oval having a black square withinthe oval. The indicators are located on the deployment mechanism suchthat when assembled, the indicators 411 and 419 may be seen through slot406 in housing 401.

The proximal portion 410 includes a stationary portion 410 b and arotating portion 410 a. The proximal portion 410 includes a channel 412that runs part of the length of stationary portion 410 b and the entirelength of rotating portion 410 a. The channel 412 is configured tointeract with a protrusion 417 on an interior portion of housingcomponent 401 a (FIGS. 28A and 28B). During assembly, the protrusion 417on housing component 401 a is aligned with channel 412 on the stationaryportion 410 b and rotating portion 410 a of the deployment mechanism403. The proximal portion 410 of deployment mechanism 403 is slid withinhousing component 401 a until the protrusion 417 sits within stationaryportion 410 b (FIG. 28C). Assembled, the protrusion 417 interacts withthe stationary portion 410 b of the deployment mechanism 403 andprevents rotation of stationary portion 410 b. In this configuration,rotating portion 410 a is free to rotate within housing component 401 a.

Referring back to FIGS. 27A-27D, the rotating portion 410 a of proximalportion 410 of deployment mechanism 403 also includes channels 413 a,413 b, and 413 c. Channel 413 a includes a first portion 413 a 1 that isstraight and runs perpendicular to the length of the rotating portion410 a, and a second portion 413 a 2 that runs diagonally along thelength of rotating portion 410 a, downwardly toward a proximal end ofthe deployment mechanism 403. Channel 413 b includes a first portion 413b 1 that runs diagonally along the length of the rotating portion 410 a,downwardly toward a distal end of the deployment mechanism 403, and asecond portion that is straight and runs perpendicular to the length ofthe rotating portion 410 a. The point at which first portion 413 a 1transitions to second portion 413 a 2 along channel 413 a, is the sameas the point at which first portion 413 b 1 transitions to secondportion 413 b 2 along channel 413 b. Channel 413 c is straight and runsperpendicular to the length of the rotating portion 410 a. Within eachof channels 413 a, 413 b, and 413 c, sit members 414 a, 414 b, and 414 crespectively. Members 414 a, 414 b, and 414 c are movable withinchannels 413 a, 413 b, and 413 c. Members 414 a, 414 b, and 414 c alsoact as stoppers that limit movement of rotating portion 410 a, whichthereby limits axial movement of the shaft 404.

FIG. 30 shows a cross-sectional view of deployment mechanism 403. Member414 a is connected to the distal portion 409 of the deployment mechanism403. Movement of member 414 a results in retraction of the distalportion 409 of the deployment mechanism 403 to within the proximalportion 410 of the deployment mechanism 403. Member 414 b is connectedto a pusher component 418. The pusher component 418 extends through thedistal portion 409 of the deployment mechanism 403 and extends into aportion of hollow shaft 404. The pusher component is involved indeployment of a shunt from the hollow shaft 404. An exemplary pushercomponent is a plunger. Movement of member 414 b engages pusher 418 andresults in pusher 418 advancing within hollow shaft 404.

Reference is now made to FIGS. 31A-37B, which accompany the followingdiscussion regarding deployment of a shunt 415 from deployment device400. FIG. 31A shows deployment device 400 in a pre-deployment orinsertion configuration. In this configuration, shunt 415 is loadedwithin hollow shaft 404 (FIG. 31B). As shown in FIG. 31B, shunt 415 isonly partially within shaft 404, such that a portion of the shunt isexposed. However, the shunt 415 does not extend beyond the end of theshaft 404. In other embodiments, the shunt 415 is completely disposedwithin hollow shaft 404. The shunt 415 is loaded into hollow shaft 404such that the shunt abuts pusher component 418 within hollow shaft 404.

In the pre-deployment or insertion configuration, the distal portion 401b of the housing 401 is in an extended position, with spring 421 in arelaxed state (FIG. 31A). Additionally, in the pre-deploymentconfiguration, the shaft 404 is fully disposed within the sleeve 430 ofthe distal portion 401 b of the housing 401 (FIG. 31B). Pusher 418 abutsshunt 415 (FIG. 31B).

The deployment mechanism 403 is configured such that member 414 a abutsa distal end of the first portion 413 a 1 of channel 413 a, and member414 b abut a proximal end of the first portion 413 b 1 of channel 413 b(FIG. 31C). In this configuration, the ready indicator 411 is visiblethrough slot 406 of the housing 401, providing feedback to an operatorthat the deployment mechanism is in a configuration for deployment of anintraocular shunt from the deployment device 400 (FIG. 31D). In thisconfiguration, the device 400 is ready for insertion into an eye(insertion configuration or pre-deployment configuration).

FIGS. 32A-32B show device 400 in the insertion configuration andinserted into an eye 440. FIG. 32A is a magnified view of the positionof the distal portion 401 b relative to the proximal portion 401 a inthe insertion configuration. FIG. 32B is a magnified view of the sleeve430 of device 400 inserted into the eye. Any of a variety of methodsknown in the art may be used to insert some embodiments of the deviceinto an eye. In certain embodiments, some embodiments of the device maybe inserted into the eye using an ab externo approach (entering throughthe conjunctiva) or an ab interno approach (entering through thecornea). In particular embodiment, the approach is an ab internoapproach as shown Yu et al. (U.S. Pat. No. 6,544,249 and U.S. Pat. Pub.No. 2008/0108933) and Prywes (U.S. Pat. No. 6,007,511), the content ofeach of which is incorporated by reference herein in its entirety.

FIGS. 32A-32B shows an ab interno approach for insertion of device 400into the eye 440. In FIG. 32B, protrusion 431 at the distal end of thesleeve 430 has been advanced across the anterior chamber 441 to theanterior chamber angle 443 on the opposite side of the eye 440 fromwhich the device entered the eye 440. FIG. 32B shows protrusion 431 andsleeve 430 fitted within the anterior chamber angle 443 of the eye 440,thus re-opening the partially or completely closed anterior chamberangle 443. Further, FIG. 32B illustrates that the protrusion 431 at thedistal end of the sleeve 430 has been advanced across the anteriorchamber 441 to the sclera 442 on the opposite side of the eye 440 fromwhich the device entered the eye 440. FIG. 32B shows protrusion 431 andsleeve 430 fitted within the anterior chamber angle 443 of the eye 440.Such insertion and placement is accomplished without the use of anoptical apparatus that contacts the eye, such as a goniolens. In certainembodiments this insertion is accomplished without the use of anyoptical apparatus.

Insertion without the use of an optical apparatus that contacts the eye,or any optical apparatus, is possible because of various features of thedevice described above and reviewed here briefly. The shape of theprotrusion 431 is such that it corrects for an insertion angle that istoo steep or too shallow, ensuring that the sleeve 430 is fitted intothe anterior chamber angle of the eye, the place for proper deploymentof an intraocular shunt. Further, the shape of the protrusion providesadequate surface area at the distal end of sleeve 430 to prevent enoughforce from being generated at the distal end of sleeve 430 that wouldresult in sleeve 430 entering an improper portion of the sclera 442 (ifthe insertion angle is too shallow) or entering an improper portion ofthe iris 444 (if the insertion angle is too steep). Additionally, sincethe hollow shaft 404 is fully disposed within the sleeve 430, it cannotpierce tissue of the eye until it is extended from the sleeve 430. Thus,if the insertion angle is too shallow or too steep, the protrusion 431can cause movement and repositioning of the sleeve 430 so that thesleeve 430 is properly positioned to fit in the anterior chamber angleof the eye for proper deployment of the shunt. Due to these features ofdevice 400, some embodiments of the device provide for deployingintraocular shunts without use of an optical apparatus that contacts theeye, preferably without use of any optical apparatus.

Once the device has been inserted into the eye and the protrusion 431and the sleeve 430 are fitted within the anterior chamber angle of theeye, the hollow shaft 404 may be extended from within the sleeve 430.Referring now to FIG. 33A which show extension of the hollow shaft 404from within the sleeve 430, which is accomplished by partial retractionof distal portion 401 b of housing 401 to within proximal portion 401 aof housing 401 (FIG. 33A).

Retraction of the distal portion 401 b of housing 401 to within proximalportion 401 a of housing 401 is accomplished by an operator continuingto apply force to advance device 400 after the protrusion 431 and thesleeve 430 are fitted within the anterior chamber angle of the eye. Thesurface area of protrusion 431 prevents the application of theadditional force by the operator from advancing sleeve 430 into thesclera 434. Rather, the additional force applied by the operator resultsin engagement of spring mechanism 420 and compression of spring 421within spring mechanism 420. Compression of spring 420 results inretraction of distal portion 401 b of housing 401 to within proximalportion 401 a of housing 401. The amount of retraction of distal portion401 b of housing 401 to within proximal portion 401 a of housing 401 islimited by member 422 that acts as a stopper and limits axial retractionof distal portion 401 b within proximal portion 401 a.

Retraction of distal portion 401 b of housing 401 to within proximalportion 401 a of housing 401 results in extension of hollow shaft 404,which now extends beyond the distal end of sleeve 430 and advancesthrough the sclera 442 to an area of lower pressure than the anteriorchamber (see e.g., FIG. 33B).

In FIG. 33A, a distal end of the shaft is shown to be located within theintra-Tenon's space. Within an eye, there is a membrane known as theconjunctiva, and the region below the conjunctiva is known as thesubconjunctival space. Within the subconjunctival space is a membraneknown as Tenon's capsule. Below Tenon's capsule there are Tenon'sadhesions that connect the Tenon's capsule to the sclera. The spacebetween Tenon's capsule and the sclera where the Tenon's adhesionsconnect the Tenon's capsule to the sclera is known as the intra-Tenon'sspace. This figure is exemplary and depicts only one embodiment for alocation of lower pressure. It will be appreciated that some embodimentsof the device may deploy shunts to various different locations of theeye and are not limited to deploying shunts to the intra-Tenon's spaceis shown by way of example in this figure. In this configuration, theshunt 415 is still completely disposed within the shaft 404.

The distal end of shaft 404 may be beveled to assist in piercing thesclera and advancing the distal end of the shaft 404 through the sclera.In this figure, the distal end of the shaft 404 is shown to have adouble bevel (See also FIG. 31B). The double bevel provides an angle atthe distal end of the shaft 404 such that upon entry of the shaft intointra-Tenon's space, the distal end of shaft 404 will by parallel withTenon's capsule and will thus not pierce Tenon's capsule and enter thesubconjunctival space. This ensures proper deployment of the shunt suchthat a distal end of the shunt 415 is deployed within the intra-Tenon'sspace, rather than deployment of the distal end of the shunt 415 withinthe subconjunctival space. Changing the angle of the bevel allows forplacement of shunt 415 within other areas of lower pressure than theanterior chamber, such as the subconjunctival space. It will beunderstood that FIG. 33A-33B is merely one embodiment of where shunt 415may be placed within the eye, and that some embodiments of the deviceare not limited to placing shunts within intra-Tenon's space and may beused to place shunts into many other areas of the eye, such as Schlemm'scanal, the subconjunctival space, the episcleral vein, or thesuprachoroidal space.

Referring to FIG. 33B, as noted above, retraction of distal portion 401b of housing 401 to within proximal portion 401 a of housing 401 resultsin extension of hollow shaft 404, which now extends beyond the distalend of sleeve 430 and advances through the sclera 442. In accordancewith some embodiments, the rigidity of the sleeve 430 holds hollow shaft404 in a straight configuration. Upon its exposure from the sleeve 430,hollow shaft 404 reverts to its pre-bent configuration, which bendminors the angle or arc of the sclera. Such a pre-bend allows the hollowshaft 404 to follow the scleral spur down along the sclera in aself-guided manner to the suprachoroidal space. Generally, the bend inthe hollow shaft 404 will be from about 5° degrees to about 70° degrees.

Additionally, the flexibility of the hollow shaft 404 allows it tocontinually bend and flex in response to the anatomy as the hollow shaft404 advances from the sleeve 430. The hollow shaft 404 is advanced untila distal portion of the hollow shaft 404 is within the suprachoroidalspace. In this configuration, the shunt 415 is still completely disposedwithin the shaft 404. The distal end of hollow shaft 404 may be beveledto assist in piercing the sclera and advancing the distal end of thehollow shaft 404 through the sclera.

At this point, an amount of BSS/steroid or other drug can be optionallyinjected through the hollow shaft and implant into a lower end of thetarget space to create a primed space for outflow and to deliverantifibrotic or other drugs to that new drainage space.

Reference is now made to FIGS. 34A to 34D. After extension of hollowshaft 404 from sleeve 430, the shunt 415 may be deployed from the device400. The deployment mechanism 403 is a two-stage system. The first stageis engagement of the pusher component 418 and the second stage isretraction of the distal portion 409 of deployment mechanism 403 towithin the proximal portion 410 of the deployment mechanism 403.Rotation of the rotating portion 410 a of the proximal portion 410 ofthe deployment mechanism 403 sequentially engages the pusher componentand then the retraction component.

In the first stage of shunt deployment, the pusher component is engagedand the pusher partially deploys the shunt from the deployment device.During the first stage, rotating portion 410 a of the proximal portion410 of the deployment mechanism 403 is rotated, resulting in movement ofmembers 414 a and 414 b along first portions 413 a 1 and 413 b 1 inchannels 413 a and 413 b. Since the first portion 413 a 1 of channel 413a is straight and runs perpendicular to the length of the rotatingportion 410 a, rotation of rotating portion 410 a does not cause axialmovement of member 414 a. Without axial movement of member 414 a, thereis no retraction of the distal portion 409 to within the proximalportion 410 of the deployment mechanism 403. Since the first portion 413b 1 of channel 413 b runs diagonally along the length of the rotatingportion 410 a, upwardly toward a distal end of the deployment mechanism403, rotation of rotating portion 410 a causes axial movement of member414 b toward a distal end of the device. Axial movement of member 414 btoward a distal end of the device results in forward advancement of thepusher component 418 within the hollow shaft 404. Such movement ofpusher component 418 results in partially deployment of the shunt 415from the shaft 404.

FIGS. 34A-34C show schematics of the deployment mechanism at the end ofthe first stage of deployment of the shunt from the deployment device.FIGS. 34A-34B show the shaft in a straight configuration, as if it iswithin the stiff outer sleeve. As is shown FIG. 34A, members 414 a and414 b have finished traversing along first portions 413 a 1 and 413 b 1of channels 413 a and 413 b. Additionally, pusher component 418 hasadvanced within hollow shaft 404 (FIG. 34B), and shunt 415 has beenpartially deployed from the hollow shaft 404 (FIG. 34C). As is shown inFIG. 34D, a portion of the shunt 415 extends beyond an end of the shaft404.

FIGS. 35A-35B show device 400 at the end of the first stage ofdeployment of the shunt 415 from device 400 and into the eye 440. Thisfigure shows that the distal portion 401 b of the housing 401 remainsretracted within the proximal portion 401 a of the housing 401, and thatthe hollow shaft 404 remains extended from the sleeve 430. As is shownin these figures, pusher 418 has been engaged and, which allows shunt415 to be deployed from the hollow shaft 404. A portion of the shunt 415can extend beyond an end of the shaft 404 and be located in theintra-Tenon's space.

Reference is now made to FIGS. 36A-36D. In the second stage of shuntdeployment, the retraction component of deployment mechanism is engagedand the distal portion of the deployment mechanism is retracted towithin the proximal portion of the deployment mechanism, therebycompleting deployment of the shunt from the deployment device. Duringthe second stage, rotating portion 410 a of the proximal portion 410 ofthe deployment mechanism 403 is further rotated, resulting in movementof members 414 a and 414 b along second portions 413 a 2 and 413 b 2 inchannels 413 a and 413 b. Since the second portion 413 b 2 of channel413 b is straight and runs perpendicular to the length of the rotatingportion 410 a, rotation of rotating portion 410 a does not cause axialmovement of member 414 b. Without axial movement of member 414 b, thereis no further advancement of pusher 418. Since the second portion 413 a2 of channel 413 a runs diagonally along the length of the rotatingportion 410 a, downwardly toward a proximal end of the deploymentmechanism 403, rotation of rotating portion 410 a causes axial movementof member 414 a toward a proximal end of the device. Axial movement ofmember 414 a toward a proximal end of the device results in retractionof the distal portion 409 to within the proximal portion 410 of thedeployment mechanism 403. Retraction of the distal portion 409, resultsin retraction of the hollow shaft 404. Since the shunt 415 abuts thepusher component 418, the shunt remains stationary as the hollow shaft404 retracts from around the shunt 415. The hollow shaft 404 retractscompletely to within the sleeve 430 of the distal portion 401 b of thehousing 401. During both stages of the deployment process, the sleeve430 remains stationary and in a fixed position.

Referring to FIGS. 36A-36D, which show schematics of the deploymentmechanism at the end of the second stage of deployment of the shunt fromthe deployment device. As is shown in FIG. 36A, members 414 a and 414 bhave finished traversing along second portions 413 a 2 and 413 b 2 ofchannels 413 a and 413 b. Additionally, distal portion 409 has retractedto within proximal portion 410, thus resulting in retraction of thehollow shaft 404 to within the sleeve 430. FIG. 36A shows the shaft in astraight configuration, after it has been retracted into the stiff outersleeve.

FIGS. 36B and 36C show a schematic of the device 400 in the eye 430after the second stage of deployment has been completed. FIG. 36B showsthat the distal portion 401 b of the housing 401 remains retractedwithin the proximal portion 401 a of the housing 401. As is shown inFIGS. 36B and 36C, shaft 404 has withdrawn through the sclera 434 to befully retracted to within sleeve 430. At completion of the second stageof deployment, a distal portion of the shunt 415 has been deployed andresides in the intra-Tenon's space (see FIG. 36B) or in thesuprachoroidal space (see FIG. 36C), a middle portion of the shunt 415spans the sclera, and a proximal portion of shunt 415 has been deployedfrom shaft 404 yet still resides within sleeve 430. The proximal portionof the shunt 415 still abuts pusher 418.

Referring to FIG. 36D, in the post-deployment configuration, thedeployed indicator 419 is visible through slot 406 of the housing 401,providing feedback to the operator that the deployment mechanism 403 hasbeen fully engaged and that the deployment mechanism 403 has completedits second stage of deployment.

Referring to FIG. 37A-37B, which show schematics of the device 400 aftercompletion of deployment of the shunt 415 from the device 400 and in tothe eye 440. After completion of the second stage of the deployment bythe deployment mechanism 403, as indicated to the operator byvisualization of deployed indicator 419 through slot 406 of the housing401, the operator may pull the device 400 from the eye 440. Backwardforce by the operator reengages spring mechanism 420 and results inuncoiling of spring 421 (FIG. 37A). Uncoiling of spring 421 proceeds asthe proximal portion 401 a of housing 401 is pulled from the eye 440.Such action causes distal portion 401 b to return to its extended statewithin proximal portion 401 a of housing 401 (FIG. 37A). Continuedbackward force by the operator continues to pull the device 400 from theeye 440. As the device 400 is continued to be pulled from the eye, thesleeve 430 is also pulled backward and the proximal portion of the shunt415 is exposed from within the sleeve 430 and resides within theanterior chamber 441 of the eye 440 (FIG. 37B). The operator continuesto apply backward force until the device 400 is completely withdrawnfrom the eye 440. At this point, in some embodiments, a distal portionof the shunt 415 has been deployed and can reside in the suprachoroidalspace (see FIGS. 36C and 37B), a middle portion of the shunt 415 spansthe sclera, and a proximal portion of shunt 415 has been deployed andresides in the anterior chamber.

Three Stage Deployment Mechanism

Another embodiment by which the hollow shaft 404 may be extended fromthe sleeve 430 involves a deployment mechanism that is a three-stagemechanism. The three-stage mechanism operates similarly to the abovedescribed device that uses a spring loaded distal portion and atwo-stage deployment mechanism. In the three-stage system, the channelsof the deployment mechanism are extended to accommodate the new firststage. The newly added portion of the channels run diagonally upwardalong the length of the rotating portion toward the proximal end of thedeployment mechanism. Axial movement by the members within the channelsresults in the extension of the hollow shaft 404 from the sleeve 430.The new first stage replaces the spring loaded distal portion andresults in extension of the hollow shaft 404 from the sleeve 430. Theengagement of the pusher component 418 becomes the second stage andretraction of the distal portion 409 of deployment mechanism 403 towithin the proximal portion 410 of the deployment mechanism 403 becomesthe third stage. The second and third stages of the three-stage systemare the same as the first and second stages of the two-stage system andoperate as described above. Rotation of the rotating portion of thedistal portion of the deployment mechanism sequentially extends thehollow shaft from the sleeve, engages the pusher component and thenengages the retraction component.

Referring now to FIGS. 38A-38E, the sleeve 505 may include an edge 531at a distal end that provides resistance feedback to an operator uponinsertion of the deployment device 500 within an eye 532 of a personduring delivery of the shunt 515. Upon advancement of the device 500across an anterior chamber 533 of the eye 532, the hollow sleeve 505will eventually contact the sclera 534, providing resistance feedback toan operator that no further advancement of the device 500 is necessary.The edge 531 of the sleeve 505 prevents the shaft 504 from accidentallybeing pushed too far through the sclera 534.

Combinations of Embodiments

As will be appreciated by one skilled in the art, individual features ofsome embodiments may be used separately or in any combination.Particularly, it is contemplated that one or more features of theindividually described above embodiments may be combined into a singleshunt.

INCORPORATION BY REFERENCE

References and citations to other documents, such as patents, patentapplications, patent publications, journals, books, papers, webcontents, have been made throughout this disclosure. All such documentsare hereby incorporated herein by reference in their entirety for allpurposes.

EQUIVALENTS

The inventions may be embodied in other specific forms without departingfrom the spirit or essential characteristics thereof. The foregoingembodiments are therefore to be considered in all respects illustrativerather than limiting on the inventions described herein.

What is claimed is:
 1. A method of deploying an intraocular shunt intoan eye, the method comprising: inserting into the eye a hollow shaft,having a curved configuration and a less curved configuration, lesscurved than the curved configuration, and holding an intraocular shunt;injecting a drug into the eye; exposing the shunt, out of the shaftalong a scleral spur of the eye while the shaft is in the curvedconfiguration along the scleral spur such that the shunt forms a passagewith a proximal portion of the shunt residing in an anterior chamber ofthe eye and a distal portion of the shunt residing in the suprachoroidalspace; withdrawing the shaft, in the less curved configuration, from theeye.
 2. The method of claim 1, wherein the drug comprises a balancedsalt solution, a steroid, or an antifibrotic agent.
 3. The method ofclaim 1, wherein the injecting comprises injecting the drug into asuprachoroidal space of the eye.
 4. The method of claim 1, wherein theinjecting comprises injecting the drug into the eye through the hollowshaft and the shunt.
 5. The method of claim 1, wherein the exposingcomprises allowing the shunt to be guided along the scleral spur of theeye.
 6. The method of claim 1, wherein the eye comprises a cornea, andthe inserting comprises inserting the hollow shaft through the cornea.7. The method of claim 1, wherein the eye comprises a corneal limbus,and the inserting comprises inserting the shaft into the eye posteriorto the corneal limbus.
 8. The method of claim 1, wherein inserting thehollow shaft comprises moving at least a portion of the shaft out of ahollow sleeve, such that the hollow shaft changes from the less curvedconfiguration in the sleeve to the curved configuration out of thesleeve.
 9. The method of claim 1, wherein inserting the hollow shaftcomprises forming a curved pathway along a scleral spur.
 10. The methodof claim 1, wherein during the withdrawing, the shaft is withdrawn intoa hollow sleeve and changes from the curved configuration to the lesscurved configuration.
 11. The method of claim 1, wherein the shuntcomprises a pharmaceutical or biological agent deliverable to the eye.12. The method of claim 11, wherein the pharmaceutical or biologicalagent comprises a coating on a surface of the shunt.
 13. The method ofclaim 11, wherein a portion of the shunt is impregnated with thepharmaceutical or biological agent.
 14. The method of claim 11, whereinthe pharmaceutical or biological agent comprises a time-releasepharmaceutical or biological agent.
 15. A method of deploying anintraocular shunt into an eye, the method comprising: inserting into theeye a hollow shaft, having a curved configuration and a less curvedconfiguration, less curved than the curved configuration, and holding anintraocular shunt; injecting a drug into the eye; exposing the shunt outof the shaft, while the shaft is in the curved configuration, such thatthe shunt forms a curved passage with a proximal portion of shuntresiding in an anterior chamber of the eye and a distal portion of theshunt residing in the suprachoroidal space; and withdrawing the shaft,in the less curved configuration, from the eye.
 16. The method of claim15, wherein the drug comprises a balanced salt solution, a steroid, oran antifibrotic agent.
 17. The method of claim 15, wherein the injectingcomprises injecting the drug into a suprachoroidal space of the eye. 18.The method of claim 15, wherein the injecting comprises injecting thedrug into the eye through the hollow shaft and the shunt.
 19. The methodof claim 15, wherein the eye comprises a cornea, and the insertingcomprises inserting the hollow shaft through the cornea.
 20. The methodof claim 15, wherein the eye comprises a corneal limbus, and theinserting comprises inserting the shaft into the eye posterior to thecorneal limbus.
 21. The method of claim 15, wherein inserting the hollowshaft comprises moving at least a portion of the shaft out of a hollowsleeve, such that the hollow shaft changes from the less curvedconfiguration in the sleeve to the curved configuration out of thesleeve.
 22. The method of claim 15, wherein inserting the hollow shaftcomprises forming a curved pathway along a scleral spur.
 23. The methodof claim 15, wherein during the withdrawing, the shaft is withdrawn intoa hollow sleeve and changes from the curved configuration to the lesscurved configuration.
 24. The method of claim 15, wherein the shuntcomprises a pharmaceutical or biological agent deliverable to the eye.25. The method of claim 24, wherein the pharmaceutical or biologicalagent comprises a coating on a surface of the shunt.
 26. The method ofclaim 24, wherein a portion of the shunt is impregnated with thepharmaceutical or biological agent.
 27. The method of claim 24, whereinthe pharmaceutical or biological agent comprises a time-releasepharmaceutical or biological agent.